Qurani-kərim və balıq

Terrett et al. (1994) studied linkage between microsatellite DNA markers and HOS in 7 families. In 5, linkage between HOS and markers on 12q was found, whereas the 2 remaining families, phenotypically indistinguishable from the others, did not show this linkage. Analysis of the family data with the computer program HOMOG indicated that HOS is a heterogeneous disorder. In the five 12q-linked families, Terrett et al. (1994) narrowed the assignment to a 21-cM interval in the distal region.

ORA-06503: PL/SQL: Function returned without value

An important thing regarding function, you would agree with me that, at least once a PL/SQL developer must have heard that “A function MUST ALWAYS RETURN a VALUE of proper datatype” . Having been said that a million times on various platforms, still developers make this mistake.

ORA-06503: PL/SQL: Function returned without value
Cause: A call to PL/SQL function completed, but no RETURN statement was executed.
Action: Rewrite PL/SQL function, making sure that it always returns a value of a proper type.

DB version : 11.2.0.2.0

Let’s see the various scenarios of this error :

Without a RETURN statement in the function body and without exception handler(most stupid way):

SQL> set serveroutput on; SQL> CREATE OR REPLACE FUNCTION f_test(i_val NUMBER) 2 RETURN NUMBER AS 3 o_val NUMBER; 4 BEGIN 5 SELECT 100 / i_val 6 INTO o_val 7 FROM DUAL; 8 END; 9 / Function created SQL> select f_test(100) from dual; select f_test(100) from dual ORA-06503: PL/SQL: Function returned without value ORA-06512: at "F_TEST", line 8

Now, in the above code, the mathematical logic was correct, hence there was no SQL error to override the PL/SQL error. Let’s see how ORA-01476 will override the ORA-06503 error.

SQL> CREATE OR REPLACE FUNCTION f_test(i_val NUMBER) 2 RETURN NUMBER AS 3 o_val NUMBER; 4 BEGIN 5 SELECT 100 / i_val 6 INTO o_val 7 FROM DUAL; 8 END; 9 / Function created SQL> select f_test(0) from dual; select f_test(0) from dual ORA-01476: divisor is equal to zero ORA-06512: at "F_TEST", line 5

Well, that’s quite obvious, isn’t it?

2. Without a RETURN statement in the exception handler(most common mistake) :

SQL> CREATE OR REPLACE FUNCTION f_test(i_val NUMBER) 2 RETURN NUMBER AS 3 o_val NUMBER; 4 BEGIN 5 SELECT 100 / i_val 6 INTO o_val 7 FROM DUAL; 8 9 RETURN o_val; 10 11 EXCEPTION 12 WHEN OTHERS THEN 13 NULL; 14 END; 15 / Function created SQL> select f_test(0) from dual; select f_test(0) from dual ORA-06503: PL/SQL: Function returned without value ORA-06512: at "F_TEST", line 14

This is somewhat important to share.

EXCEPTION WHEN OTHERS THEN NULL;
–> is itself a bug in the code waiting for its chance to break the code.

At least a good developer would remember that WHEN OTHERS should be always followed by a RAISE. Re-raising the error would show us the root cause, rather than the confusing “ORA-06503: PL/SQL: Function returned without value” error.

SQL> CREATE OR REPLACE FUNCTION f_test(i_val NUMBER) 2 RETURN NUMBER AS 3 o_val NUMBER; 4 BEGIN 5 SELECT 100 / i_val 6 INTO o_val 7 FROM DUAL; 8 9 RETURN o_val; 10 11 EXCEPTION 12 WHEN OTHERS THEN 13 NULL; 14 RAISE; 15 END; 16 / Function created SQL> select f_test(0) from dual; select f_test(0) from dual ORA-01476: divisor is equal to zero ORA-06512: at "F_TEST", line 14

Now let’s put a RETURN statement at required places and the code should work fine without any error :

SQL> CREATE OR REPLACE FUNCTION f_test(i_val NUMBER) 2 RETURN NUMBER AS 3 o_val NUMBER; 4 BEGIN 5 SELECT 100 / i_val 6 INTO o_val 7 FROM DUAL; 8 9 RETURN o_val; 10 11 EXCEPTION 12 WHEN OTHERS THEN 13 DBMS_OUTPUT.PUT_LINE('Came inside Exception handler'); 14 RETURN 0; 15 END; 16 / Function created SQL> select f_test(0) from dual; F_TEST(0) ---------- 0 Came inside Exception handler

A function MUST ALWAYS RETURN a value of proper datatype, no matter from the body or exception.
We must do something with the error not just return junk. We must RAISE/log error and handle it, do something about the error so that underlying process has no impact.
Lastly, not to forget, EXCEPTION WHEN OTHERS THEN NULL; –> is itself a bug in the code waiting for its chance to break the code.

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Qurani-kərim və balıq

Sual: Hədislərə və məzhəbimizin hökmünə baxmadan balıq yeməyin caiz olduğu Qurandan məlum ola bilər?

CAVAB

Yalnız Qurana baxaraq anlamaq qeyri-mümkündür. Qurani-Kərimdə məalən buyurulur ki:

“Təzə ət yeməyiniz və zinət çıxartmağınız üçün dənizi əmrinizə verən Odur” (Nəhl 14)

Hənəfi məzhəbinə görə təzə ət deyərkən yeyilməyən dəniz heyvanları deyil, yalnız balıq və balıq şəklində olanlardır.

Hansı heyvanların necə yeyiləcəyi də belə bildirilir:

“Murdar, qan, donuz əti və Allahdan başqası adına kəsilənlər sizə haram edildi. Hələ ölmədən kəsdiyimiz xaric, boğulmuş, vurulmuş, düşmüş, buynuzlanmış və canavar tərəfindən parçalanmış heyvanlar haramdır.” (Maidə 3)

Davamındakı ayədə də, kəsərkən Allah adının xatırlanması, yəni Bəsmələ çəkilməsi bildirilir.

Murdar, boğazlanmadan, dinə uyğun kəsilmədən ölən heyvandır, leşdir. Bir heyvan o birini öldürərsə, dinə uyğun boğazlanmadığı üçün yeyilməz. Ayəyə baxan zaman, balığın da boğazlanması lazım olduğu aydın olur. Amma balıqları heç kim kəsmir. Üstəlik bəsmələ çəkmədən də tutula bilir. Ayədən anladığımıza görə hərəkət etsək, balığı kəsmədən və Bəsmələ çəkmədən yemək caiz olmaz. Ancaq Peyğəmbər əfəndimiz açıqlayır, “Balıqları kəsmək lazım deyil” hətta “ Bəsmələ çəkmək də lazım deyil” buyurur.

Balıqları dinamitlə və ya başqa bir şeylə öldürəndə yenə yeyilir. Hətta bir balıq o birini yesə, hər iki balıq da yeyilir. Halbuki, aslan bir maralı parçalasa, o maral yeyilməz. Peyğəmbər əfəndimizin açıqlaması olmadan bunları Qurani-Kərimdən anlamaq mümkün olmaz.

Ayədə qanın da haram olduğu bildirilir. Dalaq da qandır. Ayədə baxaraq dalaq yeməyin də haram olduğunu söyləyən cahillər olmuşdur. Peyğəmbər əfəndimiz iki qanın halal olduğunu bildirmişdir. Bu iki qanın biri dalaq, o biri də ciyərdir.

Peyğəmbər əfəndimiz, “Dənizin suyu təmizdir, murdarı (bir səbəblə öldürülmüş olanı) halaldır” və “Özbaşına ölən, su üstünə çıxan balığı yemə, su çəkildikdən sonra açıqda qalaraq ölmüşsə onu ye! Belə bir səbəblə dənizdə öləni də ye!” buyurdu.

Suyun içində özbaşına ölüb, qarnı üst tərəfdə dayanan balıq yeyilməz. Lakin, cərəyan, tor, dərman, zəlzələ, dinamit və ya hər hansı bir maddəylə ölən hər balıq yeyilir. Suyun çəkilib quruması ilə, çox istidən və ya çox soyuqdan ölən balıq və ya quşlar tərəfindən öldürülən, su içində bağlı saxlanılmaqla ölən, buz arasında sıxışaraq ölən balıqlar yeyilir. Dəniz içində ölən və ya sudan çıxarılmadan çomaqla vurulub öldürülən və ya bıçaqla başı kəsilən balıqlar yeyilir. Təmiz olmayan suların içindəki balıqları yuyub yemək caizdir. Ovlanan bir balığın içindən çıxan balıq, sağlamdırsa yeyilir.

Sual: Bəsmələsiz tutulan balıq yeyilir?

CAVAB

Balıq tutanın Müsəlman olması və Bəsmələ ilə tutması şərt deyil.

Sual: İçini təmizləmədən kilkə balığını qurudur, sardinanın də şorabasını düzəldirik. Belə balıqları yeməkdə zərər vardır?

CAVAB

İçini təmizləmək lazımdır. (Tahtavi)

Sual: Suda ölən balığı yeməkdə bir zərər vardır?

CAVAB

Balıq özbaşına ölmüşsə xəstəlikdən ölmüşdür, yeyilməz. Amma bir yerə sıxışaraq və ya buz arasında qalaraq, ya da elektiriklə filan ölmüşdürsə yeyilir.

Sual: Qarmaqla balıq tutmanın dinimizdə hökmü nədir?

CAVAB

Qarmaqla balıq tutmaqda zərər yoxdur. Dinamitlə və s. öldürmək caizdir. Bıçaqla kəsərək öldürülsə də yeyilir. Qoyunları da bıçaqla kəsmək onlara əziyyət olmaz.

Sual: İçi təmizlənmədən düzəlmiş konservanı sonradan yeyərkən içi təmizlənərsə yemək caizdir?

CAVAB

Bəli caizdir. İçi təmizlənmədən bişirilən balıq yeyilməz. Lakin şorabasının içi təmizlənərək yeyilir.

Sual: Balıq canlı ikən başını kəsib təmizləmək caiz olar?

CAVAB

Ölmədən əvvəl başını kəsmək uyğun deyildir. Kəsilərsə də yemək caizdir.

Sual: Dərmanla öldürülən balığı yemək caizdir?

CAVAB

İnsana zərər verməzsə caizdir.

Kürü

Sual: Balıqdan çıxan kürü yeyilir?

CAVAB

Yeyilir. (Bəriqa)

Oram növünü necə bilirəm

– Absent thumb [UMLS: C3278811 HPO: HP:0009777] [HPO: HP:0009777]
– Bifid thumb [SNOMEDCT: 51219000] [UMLS: C4082168, C0265608 HPO: HP:0009944] [HPO: HP:0009944]
– Triphalangeal thumb [SNOMEDCT: 205308004] [ICD10CM: Q74.0] [UMLS: C0241397 HPO: HP:0001199] [HPO: HP:0001199]
– Carpal bone anomalies [UMLS: C1840535 HPO: HP:0001191] [HPO: HP:0001191]
– Upper extremity phocomelia [UMLS: C1840536]
– Radial-ulnar anomalies [UMLS: C1840537]
– Asymmetric involvement [UMLS: C1840538]

MOLECULAR BASIS
– Caused by mutations in the T-Box 5 gene (TBX5, 601620.0001)

▼ TEXT

A number sign (#) is used with this entry because of evidence that Holt-Oram syndrome (HOS) is caused by heterozygous mutation in the TBX5 gene (601620) on chromosome 12q24.

▼ Description

Holt-Oram syndrome is an autosomal dominant disorder characterized by abnormalities of the upper limbs and shoulder girdle, associated with a congenital heart lesion. The typical combination is considered to be a triphalangeal thumb with a secundum atrial septal defect (ASD), but there is a great range in the severity of both the heart and skeletal lesions (summary by Hurst et al., 1991).

▼ Clinical Features

Although the abnormality of the upper extremities is more extensive in some cases, the characteristic findings in the Holt-Oram syndrome are thumb anomaly and atrial septal defect. The thumb may be absent or may be a triphalangeal, nonopposable, finger-like digit. The thumb metacarpal has both a proximal and a distal epiphyseal ossification center (Temtamy and McKusick, 1978).

This syndrome was first clearly described by Holt and Oram (1960), who observed atrial septal defect in members of 4 generations of a family, associated with ‘a congenital anomaly of the thumbs which lay in the same plane as the fingers, their terminal phalanges being curved inwards.’ McKusick (1961) reported mother and daughter with atrial septal defect and absent or triphalangeal, fingerlike thumb. In 1966 the daughter gave birth to a male infant with upper extremity phocomelia and ventricular septal defect (VSD). The involvement of the arm was more extensive and the cardiovascular involvement more varied in the families described by Lewis et al. (1965) and Harris and Osborne (1966) than in the family of Holt and Oram (1960). However, it is not certain that these represented a separate mutation (McKusick, 1966). The family reported by Kuhn et al. (1963) may be an example of the Lewis type of heart-hand syndrome.

Lenz (1968) noted that the involvement of the arms in the Holt-Oram syndrome can be sufficiently severe to simulate thalidomide embryopathy.

Boehme and Shotar (1989) described a Jordanian family of normal intelligence in which members of 3 generations had complex malformations of the arms combined with variably expressed congenital heart disease. Because of the pedigree pattern, which included 1 instance of male-to-male transmission, they suggested autosomal dominant inheritance, but concluded that the disorder was distinct from HOS.

Poznanski et al. (1970) pointed out that carpal abnormalities, e.g., extra carpal bones, are more specific for the Holt-Oram syndrome than are changes in the thumb. Posteriorly and laterally, protuberant medial epicondyles of the humerus were seen in several patients. The left side was more severely affected in 27 of 39 cases (Smith et al., 1979). Cardiac involvement may be absent in patients with limb defects; 5 of 39 had normal clinical and EKG findings despite typical limb defects (Smith et al., 1979). Although a secundum atrial septal defect is most common, a wide variety of other cardiac defects occur, including ventricular septal defects and mitral valve prolapse. Patients with only limb defects may bear offspring with the complete syndrome.

Glauser et al. (1989) described a family in which the father had atrial septal defect and a hypoplastic thumb, and a son had triphalangeal thumb and syndactyly of digits 1 and 2 on the left with aplasia of the right thumb, and hypoplastic left heart syndrome with large atrial septal defect, coarctation of the aorta, patent ductus arteriosus (PDA), severe aortic stenosis, small left ventricle, and pulmonary hypertension. An older sister of this son had atrial septal defect but no clinically or radiologically apparent abnormalities of the upper limbs.

Moens et al. (1993) reported a 4-generation family with HOS. In addition to the typical changes in the thumb and atrial septal defect, there was postaxial/central polydactyly in some family members.

Basson et al. (1994) reported 2 extensively affected kindreds with HOS showing linkage to chromosome 12. The first family was previously reported by Gall et al. (1966). Of 49 at-risk family members in 5 generations, 26 (11 male and 15 female) were affected. Each affected member was the offspring of an affected parent, thereby confirming the high penetrance of the disease gene. All affected members had some skeletal abnormalities, although many of these were subtle and detected only by radiography. Skeletal deformities generally manifested as deformities of the thenar and carpal bones, occasionally in association with mildly hypoplastic clavicles and shortened radii. Thenar abnormalities included distal displacement of the thenar eminence in the presence or absence of a triphalangeal digit. Only one subject had an aplastic thumb on one side; the contralateral thumb was triphalangeal. None of the subjects had phocomelia or severe ectromelia. All affected members had cardiovascular disease. Septal defects were present in 15 of the surviving family members; 4 had atrial septal defects, 9 had ventricular septal defects, and 2 had both. The atrial septal defects were all of the ostium secundum type, except for one which involved an ostium primum defect. Four had required surgical correction of hemodynamically significant defects. One member of the family died of complications related to a complete atrioventricular canal defect. Eisenmenger syndrome, resulting from an uncorrected ventricular septal defect, was present in 1. Cardiac conduction disease, including bradycardia, atrioventricular block, atrial fibrillation, and sinus node dysfunction, was present in 11 of the surviving affected family members, and 6 required permanent pacemakers. The second family studied by Basson et al. (1994) had 18 affected members (10 male and 8 female) surviving with HOS. All had skeletal abnormalities, which were typically more severe than those found in the first family. Bilateral frank phocomelia or severe ectromelia characterized by hypoplastic humeri, radii, and clavicles, with thenar aplasia and carpal and digital deformities, was present in 7. On the other hand, congenital cardiovascular disease was milder and less frequent in the second family in which 6 had cardiac disease, all consisting of atrial septal defect of the ostium secundum type. Surgery for the septal defect had been required in 3 of these. Only one member of the family had conduction disease (incomplete right bundle branch block), and none had patent ductus arteriosus or superior vena cava anomaly, which were present in members of the first kindred. Since the 2 families showed the same linkage relationship to markers on 12q, the disorders are probably due to different mutations in the same gene, which is important to the development of both the limbs and the cardiovascular system.

Newbury-Ecob et al. (1996) reported a detailed study of a large cohort of patients that included 44 familial and 11 sporadic cases. Association of cardiac and radial abnormalities was a criterion for inclusion of familial cases. Limb defects were found in all affected persons. The thumb was the most commonly affected structure, although in 7 of 44 cases, the thumbs were normal. In most cases, the thumb defects (absence in 19/44, hypoplasia in 17/44, triphalangeal thumbs in 8/44) were associated with hypoplastic thenar or limited supination of the forearm. Radial hypoplasia (18/44) was more frequent than absence of radius (10/44). Ulnar hypoplasia occurred only in patients with radial defects. Most patients had narrow, sloping shoulders. Limb defects were always bilateral and often asymmetrical, the left side being more severely affected. Cardiac involvement was found in 95% of familial cases; secundum atrial septal defect (15) and ventricular septal defect (11) were the most common defects. In 17 of the familial cases, only ECG abnormalities were found. Both cardiac and limb abnormalities were more severe in the sporadic group. Newbury-Ecob et al. (1996) found a significant positive correlation (r = 0.49) between severity of the limb and cardiac defects. The patients with atrial septal defects had more severe limb abnormalities. Correlation between sibs was greater than that between parent and offspring.

Sletten and Pierpont (1996) described a family in which the proband had hypoplastic left thumb, hypoplastic left ventricle and endocardial cushion defect. His mother, aunt, uncle, grandfather and some other relatives had less pronounced manifestations of HOS. Analysis of the literature showed that single cardiovascular malformations (CVM) such as ASD, VSD, or PDA were reported in 125 of 189 cases (66%), and 33 patients (17.5%) had more complex cardiac defects (hypoplastic left heart, total anomalous pulmonary venous return, truncus arteriosus). Sletten and Pierpont (1996) emphasized that the proportion of severe CVM in patients with HOS has been underestimated and should be considered in counseling families with the disorder.

Kantaputra et al. (2002) described a Thai family in which the mother and 3 offspring were affected with a dominantly inherited malformation syndrome with short stature, upper limb anomaly, and minor craniofacial anomalies suggestive of HOS; however, molecular studies did not reveal any mutations in the TBX5 gene. One of the offspring, a 23-year-old man, was cardiologically asymptomatic, although echocardiography revealed he had a quadricuspid aortic valve associated with mild aortic regurgitation.

Tseng et al. (2007) reported a Taiwanese male infant with genetically confirmed HOS and right lung agenesis. He presented at birth with severe respiratory distress, sloping shoulder, and absence of bilateral thumbs and radii. Cardiac ultrasound showed atrial and ventricular septal defects, patent ductus arteriosus, and dextroposition of the heart. Chest CT scan showed absence of the right lung and bronchial tree. He also had absence of the right pulmonary artery and vein. Tseng et al. (2007) noted that pulmonary anomalies are uncommon in HOS, but may expand the phenotypic abnormalities associated with the disorder.

▼ Diagnosis

Brons et al. (1988) discussed the prenatal diagnosis of HOS in 2 pregnancies. More severe forms of the disorder were excluded early in gestation. In the first fetus, ventricular septal defect, atrial septal defect, and a minor skeletal defect were found at 22 weeks. In a second fetus in the same sibship, no structural abnormalities were discovered until the thirtieth week, when a small atrial septal defect was detected.

▼ Cytogenetics

Rybak et al. (1971) described many cases in 4 generations of a Polish family and concluded that partial deletion of the long arm of a B-group chromosome was related to the abnormality. They suggested that the single case of Ockey et al. (1967) had the Holt-Oram syndrome; a similar deletion of the long arm of a group B chromosome was present. Rybak (1981) reported that the family refused to be restudied with banding techniques.

Turleau et al. (1984) described de novo deletion of the q23-q24.2 region of chromosome 14 in a boy with arm and cardiac abnormalities possibly consistent with the Holt-Oram syndrome. In addition, he had mental retardation, synophrys, strabismus, thin upper lip, bilateral pretragian skin tags, and cryptorchidism. Using linkage studies, Ruiz et al. (1994) excluded the 14q23-q24 region as the site of the HOS gene in a Belgian family with several affected persons in 4 generations.

Kristoffersson et al. (1987) found normal high-resolution karyotypes in 3 patients: a mother, her daughter, and an unrelated woman. Yang et al. (1990) described a sporadic case of HOS associated with a de novo pericentric inversion of chromosome 20. The breakpoints in chromosome 20 were at p13 and q13.2. They suggested that the HOS mutation is located at the site of one of these breakpoints.

Basson et al. (1999) described a child with a chromosome 5;12 translocation that caused severe skeletal and composite cardiac malformations. The affected child had left arm phocomelia, right radial hypoplasia, and right thumb aplasia. Cardiac angiography demonstrated a common atrium and a complete atrioventricular canal defect.

▼ Mapping

Terrett et al. (1994) studied linkage between microsatellite DNA markers and HOS in 7 families. In 5, linkage between HOS and markers on 12q was found, whereas the 2 remaining families, phenotypically indistinguishable from the others, did not show this linkage. Analysis of the family data with the computer program HOMOG indicated that HOS is a heterogeneous disorder. In the five 12q-linked families, Terrett et al. (1994) narrowed the assignment to a 21-cM interval in the distal region.

In each of 2 extensively affected kindreds, Basson et al. (1994) demonstrated linkage of HOS to markers in the 12q2 region; combined multipoint lod score = 16.8. Judging by the location of the markers used, HOS probably is in the q21.3-q22 region.

Fryns et al. (1996) reported a family in which linkage to 12q was excluded, thus demonstrating genetic heterogeneity in the Holt-Oram syndrome.

▼ Inheritance

The Holt-Oram syndrome is inherited as an autosomal dominant trait (Hurst et al., 1991).

Braulke et al. (1991) reported a probable instance of germinal mosaicism: an unaffected man fathered 4 offspring with HOS by 3 different women.

▼ Molecular Genetics

Li et al. (1997) and Basson et al. (1997) demonstrated mutations in the TBX5 gene as the basis of Holt-Oram syndrome (see, e.g., 601620.0001-601620.0005). The dominant phenotype of HOS appears to result from haploinsufficiency of TBX5. The glu69-to-ter mutation (601620.0002) identified by Basson et al. (1997) in affected members of one kindred was predicted to encode a markedly truncated TBX5 protein that lacked most T-box residues.

Basson et al. (1999) showed that TBX5 mutations predicted to create null alleles caused substantial abnormalities in both limb and heart. In contrast, missense mutations of the TBX5 gene produced distinct phenotypes: gly80 to arg (601620.0004) caused significant cardiac malformations but only minor skeletal abnormalities, whereas 2 mutations of codon 237, arg237 to gln (601620.0003) and arg237 to trp (601620.0005), caused extensive upper limb malformations but less significant cardiac abnormalities. They noted that residue 80 is highly conserved within T-box sequences that interact with the major groove of target DNA, whereas residue 237 is located in the T-box domain that selectively binds to the minor groove of DNA.

Yang et al. (2000) analyzed 11 Chinese patients with Holt-Oram syndrome using SSCP analysis of TBX5. The authors identified 3 novel mutations, including a frameshift mutation caused by a deletion of 1 basepair (601620.0006), and 2 missense mutations (601620.0007 and 601620.0008). The patients with the frameshift mutation had more severe upper limb anomalies, including aplasia/hypoplasia of the arm and thumbs, while those with missense mutations had milder anomalies, such as absent or hypoplastic thumbs, without arm abnormalities.

In 2 unrelated families with HOS, Gruenauer-Kloevekorn and Froster (2003) found the same truncation mutation in all affected members (601620.0009). The phenotype was similar in both families and included ASD, hypoplastic deltoid muscles, and hypoplastic or absent thumbs extending to radial defects in 1 patient.

Borozdin et al. (2006) reported a Czech mother and 2 daughters who were diagnosed with Holt-Oram syndrome, in whom they identified a 2.19 to 2.27-Mb contiguous deletion encompassing the TBX5 and TBX3 (601621) genes. Clinical reexamination confirmed the presence of features of ulnar-mammary syndrome (UMS; 181450) that were previously unrecognized. Borozdin et al. (2006) noted that the contiguous deletion also included the RBM19 gene (616444), but commented that it was unlikely to contribute to or modify the phenotype since all the anomalies present in the affected individuals could be explained by either TBX5 or TBX3 haploinsufficiency.

In affected members of a 5-generation family segregating an atypical form of HOS, consisting predominantly of nonseptal cardiac defects and mild limb anomalies, Patel et al. (2012) identified a 48-kb duplication encompassing exons 2 through 9 of the TBX5 gene. The duplication, which was identified by array CGH and multiplex ligation-dependent probe amplification, segregated with the disorder in the family.

▼ Nomenclature

McKusick (1961) suggested the alternative designations atriodigital dysplasia and Holt-Oram syndrome; the latter ‘caught on.’

▼ History

An obituary of Samuel Oram (1913-1991) was provided by Davies (1992).

▼ See Also:

▼ REFERENCES

Basson, C. T., Bachinsky, D. R., Lin, R. C., Levi, T., Elkins, J. A., Soults, J., Grayzel, D., Kroumpouzou, E., Traill, T. A., Leblanc-Straceski, J., Renault, B., Kucherlapati, R., Seidman, J. G., Seidman, C. E. Mutations in human TBX5 cause limb and cardiac malformation in Holt-Oram syndrome. Nature Genet. 15: 30-35, 1997. Note: Erratum: Nature Genet. 15: 411 only, 1997. [PubMed: 8988165, related citations] [Full Text]

Basson, C. T., Cowley, G. S., Solomon, S. D., Weissman, B., Poznanski, A. K., Traill, T. A., Seidman, J. G., Seidman, C. E. The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome). New Eng. J. Med. 330: 885-891, 1994. Note: Erratum: New Eng. J. Med. 330: 1627 only, 1994. [PubMed: 8114858, related citations] [Full Text]

Basson, C. T., Huang, T., Lin, R. C., Bachinsky, D. R., Weremowicz, S., Vaglio, A., Bruzzone, R., Quadrelli, R., Lerone, M., Romeo, G., Silengo, M., Pereira, A., Krieger, J., Mesquita, S. F., Kamisago, M., Morton, C. C., Pierpont, M. E. M., Muller, C. W., Seidman, J. G., Seidman, C. E. Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations. Proc. Nat. Acad. Sci. 96: 2919-2924, 1999. [PubMed: 10077612, images, related citations] [Full Text]

Boehme, D. H., Shotar, A. O. A complex deformity of appendicular skeleton and shoulder with congenital heart disease in three generations of a Jordanian family. Clin. Genet. 36: 442-450, 1989. [PubMed: 2591070, related citations] [Full Text]

Borozdin, W., Bravo-Ferrer Acosta, A. M., Seemanova, E., Leipoldt, M., Bamshad, M. J., Unger, S., Kohlhase, J. Contiguous hemizygous deletion of TBX5, TBX3, and RBM19 resulting in a combined phenotype of Holt-Oram and ulnar-mammary syndromes. Am. J. Med. Genet. 140A: 1880-1886, 2006. [PubMed: 16892408, related citations] [Full Text]

Braulke, I., Herzog, S., Thies, U., Zoll, B. Holt-Oram syndrome in four half-siblings with unaffected parents: brief clinical report. Clin. Genet. 39: 241-244, 1991. [PubMed: 2070544, related citations] [Full Text]

Brons, J. T. J., Van Geijn, H. P., Wladimiroff, J. W., Van der Harten, J. J., Kwee, M. L., Sobotka-Plojhar, M., Arts, N. F. T. Prenatal ultrasound diagnosis of the Holt-Oram syndrome. Prenatal Diag. 8: 175-181, 1988. [PubMed: 3287365, related citations] [Full Text]

Davies, P. Obituary: S. Oram, MD, FRCP. Brit. Med. J. 304: 500 only, 1992.

Emerit, I., de Grouchy, J., Laval-Jeantet, M., Corone, P., Vernant, P. Malformations complexes des membres superieurs associees a une cardiopathie congenitale. A propos de six observations. Acta Genet. Med. Gemellol. 14: 132-163, 1965. [PubMed: 14346078, related citations]

Fryns, J. P., Bonnet, D., De Smet, L. Holt-Oram syndrome with associated postaxial and central polysyndactyly: further evidence for genetic heterogeneity in the Holt-Oram syndrome. (Letter) Genet. Counsel. 7: 323-324, 1996. [PubMed: 8985738, related citations]

Gall, J. C., Jr., Stern, A. M., Cohen, M. M., Adams, M. S., Davidson, R. T. Holt-Oram syndrome: clinical and genetic study of a large family. Am. J. Hum. Genet. 18: 187-200, 1966. [PubMed: 5904863, related citations]

Gladstone, I., Jr., Sybert, V. P. Holt-Oram syndrome: penetrance of the gene and lack of maternal effect. Clin. Genet. 21: 98-103, 1982. [PubMed: 7083616, related citations] [Full Text]

Glauser, T. A., Zackai, E., Weinberg, P., Clancy, R. Holt-Oram syndrome associated with the hypoplastic left heart syndrome. Clin. Genet. 36: 69-72, 1989. [PubMed: 2766565, related citations] [Full Text]

Gruenauer-Kloevekorn, C., Froster, U. G. Holt-Oram syndrome: a new mutation in the TBX5 gene in two unrelated families. Ann. Genet. 46: 19-23, 2003. [PubMed: 12818525, related citations] [Full Text]

Harris, L. C., Osborne, W. P. Congenital absence or hypoplasia of the radius with ventricular septal defect: ventriculo-radial dysplasia. J. Pediat. 68: 265-272, 1966.

Holt, M., Oram, S. Familial heart disease with skeletal malformations. Brit. Heart J. 22: 236-242, 1960. [PubMed: 14402857, related citations] [Full Text]

Hurst, J. A., Hall, C. M., Baraitser, M. The Holt-Oram syndrome. J. Med. Genet. 28: 406-410, 1991. [PubMed: 1870097, related citations] [Full Text]

Kantaputra, P. N., Yamasaki, K., Ishida, T., Kishino, T., Niikawa, N. A dominantly inherited malformation syndrome with short stature, upper limb anomaly, minor craniofacial anomalies, and absence of TBX5 mutations: report of a Thai family. Am. J. Med. Genet. 111: 301-306, 2002. [PubMed: 12210327, related citations] [Full Text]

Kristoffersson, U., Mineur, A., Heim, S., Mandahl, N., Mitelman, F. Normal high-resolution karyotypes in three patients with the Holt-Oram syndrome. (Letter) Am. J. Med. Genet. 28: 229-231, 1987. [PubMed: 3674114, related citations] [Full Text]

Kuhn, E., Schaaf, J., Wagner, A. Primary pulmonary hypertension, congenital heart disease and skeletal anomalies in three generations. Jpn. Heart J. 4: 205-223, 1963.

Lenz, W. Personal Communication. Munster, Germany 5/1968.

Letts, R. M., Chudley, A. E., Cumming, G., Shokeir, M. H. The upper limb-cardiovascular syndrome (Holt-Oram syndrome). Clin. Orthop. Relat. Res. 116: 149-154, 1976. [PubMed: 1277635, related citations]

Lewis, K. B., Bruce, R. A., Baum, D., Motulsky, A. G. The upper limb-cardiovascular syndrome. An autosomal dominant genetic effect on embryogenesis. JAMA 193: 1080-1086, 1965. [PubMed: 5896868, related citations]

Li, Q. Y., Newbury-Ecob, R. A., Terrett, J. A., Wilson, D. I., Curtis, A. R. J., Yi, C. H., Gebuhr, T., Bullen, P. J., Robson, S. C., Strachan, T., Bonnet, D., Lyonnet, S., Young, I. D., Raeburn, J. A., Buckler, A. J., Law, D. J., Brook, J. D. Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. Nature Genet. 15: 21-29, 1997. [PubMed: 8988164, related citations] [Full Text]

Mcfarland, J. C., Fallon, J. T. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 51-1980. New Eng. J. Med. 303: 1519-1526, 1980. [PubMed: 7432422, related citations] [Full Text]

McKusick, V. A. Medical genetics 1960. J. Chronic Dis. 14: 1-198, 1961. Fig. 45.
McKusick, V. A. Personal Communication. Baltimore, Md. 1966.

Moens, P., De Smet, L., Fabry, G., Fryns, J. P. Holt-Oram syndrome: postaxial and central polydactyly as variable manifestation in a four generation family. Genet. Counsel. 4: 277-280, 1993. [PubMed: 8110414, related citations]

Newbury-Ecob, R. A., Leanage, R., Raeburn, J. A., Young, I. D. Holt-Oram syndrome: a clinical genetic study. J. Med. Genet. 33: 300-307, 1996. [PubMed: 8730285, related citations] [Full Text]

Ockey, C. H., Feldman, G. V., MacAulay, M. E., Delaney, M. J. A large deletion of the long arm of chromosome no. 4 in a child with limb abnormalities. Arch. Dis. Child. 42: 428-434, 1967. [PubMed: 4951642, related citations] [Full Text]

Patel, C., Silcock, L., McMullan, D., Brueton, L., Cox, H. TBX5 intragenic duplication: a family with atypical Holt-Oram syndrome phenotype. Europ. J. Hum. Genet. 20: 863-86, 2012. [PubMed: 22333898, related citations] [Full Text]

Poznanski, A. K., Gall, J. C., Jr., Stern, A. M. Skeletal manifestations of the Holt-Oram syndrome. Radiology 94: 45-54, 1970. [PubMed: 5410358, related citations] [Full Text]

Ruiz, J. C., Legius, E., Cuppens, H., Moens, P., Marynen, P., Cassiman, J.-J. Exclusion of linkage to 14q23-24 in a family with Holt-Oram syndrome. Clin. Genet. 46: 257-259, 1994. [PubMed: 7820941, related citations] [Full Text]

Rybak, M., Kozlowski, K., Kleczkowska, A., Lewandowska, J., Sokolowski, J., Soltysik-Wilk, E. Holt-Oram syndrome associated with ectromelia and chromosomal aberrations. Am. J. Dis. Child. 121: 490-495, 1971. [PubMed: 5581016, related citations] [Full Text]

Rybak, M. Personal Communication. Krakow, Poland 9/7/1981.

Sahn, D. J., Goldberg, S. J., Allen, H. D., Canale, J. M. Cross-sectional echocardiographic imaging of supracardiac total anomalous pulmonary venous drainage to a vertical vein in a patient with Holt-Oram syndrome. Chest 79: 113-115, 1981. [PubMed: 7449488, related citations] [Full Text]

Sletten, L. J., Pierpont, M. E. M. Variation in severity of cardiac disease in Holt-Oram syndrome. Am. J. Med. Genet. 65: 128-132, 1996. [PubMed: 8911604, related citations] [Full Text]

Smith, A. T., Sack, G. H., Jr., Taylor, G. J. Holt-Oram syndrome. J. Pediat. 95: 538-543, 1979. [PubMed: 480027, related citations] [Full Text]

Temtamy, S. A., McKusick, V. A. The Genetics of Hand Malformations. New York: Alan R. Liss (pub.) 1978. Pp. 117-133.

Terrett, J. A., Newbury-Ecob, R., Cross, G. S., Fenton, I., Raeburn, J. A., Young, I. D., Brook, J. D. Holt-Oram syndrome is a genetically heterogeneous disease with one locus mapping to human chromosome 12q. Nature Genet. 6: 401-404, 1994. [PubMed: 8054982, related citations] [Full Text]

Tseng, Y.-R., Su, Y.-N., Lu, F. L., Jeng, S.-F., Hsieh, W.-S., Chen, C.-Y., Chou, H.-C., Peng, S. S.-F. Holt-Oram syndrome with right lung agenesis caused by a de novo mutation in the TBX5 gene. (Letter) Am. J. Med. Genet. 143A: 1012-1014, 2007. [PubMed: 17366586, related citations] [Full Text]

Turleau, C., de Grouchy, J., Chavin-Colin, F., Dore, F., Seger, J., Dautzenberg, M.-D., Arthuis, M., Jeanson, C. Two patients with interstitial del (14q), one with features of Holt-Oram syndrome: exclusion mapping of PI (alpha-1-antitrypsin). Ann. Genet. 27: 237-240, 1984. [PubMed: 6335371, related citations]

Van Regemorter, N., Haumont, D., Kirkpatrick, C., Viseur, P., Jeanty, P., Dodion, J., Milaire, J., Rooze, M., Rodesch, F. Holt Oram syndrome mistaken for thalidomide embryopathy–embryological considerations. Europ. J. Pediat. 138: 77-80, 1982. [PubMed: 7075631, related citations] [Full Text]

Yang, J., Hu, D., Xia, J., Yang, Y., Ying, B., Hu, J., Zhou, X. Three novel TBX5 mutations in Chinese patients with Holt-Oram syndrome. Am. J. Med. Genet. 92: 237-240, 2000. [PubMed: 10842287, related citations] [Full Text]

Yang, S. P., Sherman, S., Derstine, J. B., Schonberg, S. A. Holt-Oram syndrome gene may be on chromosome 20. (Abstract) Pediat. Res. 27: 137A only, 1990.

Zetterqvist, P. The syndrome of familial atrial septal defect, heart arrhythmia and hand malformation (Holt-Oram) in mother and son. Acta Paediat. 52: 115-122, 1963. [PubMed: 14003500, related citations] [Full Text]

Zhang, K.-Z., Sun, Q.-B., Cheng, T. O. Holt-Oram syndrome in China: a collective review of 18 cases. Am. Heart J. 111: 572-577, 1986. [PubMed: 3953367, related citations] [Full Text]

Marla J. F. O’Neill – updated : 10/18/2006

Carol A. Bocchini – updated : 9/14/2006
Victor A. McKusick – updated : 9/24/2002
Sonja A. Rasmussen – updated : 7/13/2000
Victor A. McKusick – updated : 4/16/1999
Victor A. McKusick – updated : 2/7/1997
Iosif W. Lurie – updated : 1/14/1997
Iosif W. Lurie – updated : 9/7/1996
Iosif W. Lurie – updated : 6/26/1996

Creation Date:
Victor A. McKusick : 6/4/1986
alopez : 04/16/2018

carol : 03/07/2018
carol : 03/06/2018
carol : 09/28/2016
carol : 09/27/2016
mgross : 06/30/2015
terry : 12/21/2012
terry : 5/10/2012
carol : 9/20/2010
wwang : 7/29/2009
terry : 6/3/2009
wwang : 7/19/2007
ckniffin : 7/17/2007
wwang : 10/20/2006
terry : 10/18/2006
carol : 9/14/2006
wwang : 10/18/2005
ckniffin : 4/30/2004
mgross : 12/10/2002
tkritzer : 9/24/2002
mcapotos : 7/19/2000
mcapotos : 7/17/2000
mcapotos : 7/14/2000
mcapotos : 7/13/2000
mgross : 4/27/1999
mgross : 4/21/1999
terry : 4/16/1999
alopez : 7/30/1998
alopez : 7/29/1997
terry : 7/7/1997
joanna : 7/7/1997
terry : 6/21/1997
terry : 2/7/1997
terry : 2/3/1997
mark : 1/15/1997
jenny : 1/14/1997
jenny : 1/8/1997
randy : 9/7/1996
carol : 6/26/1996
davew : 8/18/1994
mimadm : 5/17/1994
carol : 5/3/1994
pfoster : 4/20/1994
carol : 6/28/1993
carol : 5/5/1992

# 142900

HOLT-ORAM SYNDROME; HOS

Alternative titles; symbols

HOS1
HEART-HAND SYNDROME
ATRIODIGITAL DYSPLASIA

SNOMEDCT: 19092004; ICD10CM: Q87.2; ORPHA: 392; DO: 0060468;

Phenotype-Gene Relationships

Location	Phenotype	Phenotype MIM number	Inheritance	Phenotype mapping key	Gene/Locus	Gene/Locus MIM number
12q24.21	Holt-Oram syndrome	142900	Autosomal dominant	3	TBX5	601620

TEXT

A number sign (#) is used with this entry because of evidence that Holt-Oram syndrome (HOS) is caused by heterozygous mutation in the TBX5 gene (601620) on chromosome 12q24.

Description

Clinical Features

Lenz (1968) noted that the involvement of the arms in the Holt-Oram syndrome can be sufficiently severe to simulate thalidomide embryopathy.

Moens et al. (1993) reported a 4-generation family with HOS. In addition to the typical changes in the thumb and atrial septal defect, there was postaxial/central polydactyly in some family members.

Diagnosis

Cytogenetics

Mapping

Fryns et al. (1996) reported a family in which linkage to 12q was excluded, thus demonstrating genetic heterogeneity in the Holt-Oram syndrome.

Inheritance

The Holt-Oram syndrome is inherited as an autosomal dominant trait (Hurst et al., 1991).

Braulke et al. (1991) reported a probable instance of germinal mosaicism: an unaffected man fathered 4 offspring with HOS by 3 different women.

Molecular Genetics

Nomenclature

McKusick (1961) suggested the alternative designations atriodigital dysplasia and Holt-Oram syndrome; the latter ‘caught on.’

History

An obituary of Samuel Oram (1913-1991) was provided by Davies (1992).

REFERENCES

Basson, C. T., Bachinsky, D. R., Lin, R. C., Levi, T., Elkins, J. A., Soults, J., Grayzel, D., Kroumpouzou, E., Traill, T. A., Leblanc-Straceski, J., Renault, B., Kucherlapati, R., Seidman, J. G., Seidman, C. E. Mutations in human TBX5 cause limb and cardiac malformation in Holt-Oram syndrome. Nature Genet. 15: 30-35, 1997. Note: Erratum: Nature Genet. 15: 411 only, 1997. [PubMed: 8988165] [Full Text: https://doi.org/10.1038/ng0197-30]
Basson, C. T., Cowley, G. S., Solomon, S. D., Weissman, B., Poznanski, A. K., Traill, T. A., Seidman, J. G., Seidman, C. E. The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome). New Eng. J. Med. 330: 885-891, 1994. Note: Erratum: New Eng. J. Med. 330: 1627 only, 1994. [PubMed: 8114858] [Full Text: https://doi.org/10.1056/NEJM199403313301302]
Basson, C. T., Huang, T., Lin, R. C., Bachinsky, D. R., Weremowicz, S., Vaglio, A., Bruzzone, R., Quadrelli, R., Lerone, M., Romeo, G., Silengo, M., Pereira, A., Krieger, J., Mesquita, S. F., Kamisago, M., Morton, C. C., Pierpont, M. E. M., Muller, C. W., Seidman, J. G., Seidman, C. E. Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations. Proc. Nat. Acad. Sci. 96: 2919-2924, 1999. [PubMed: 10077612] [Full Text: https://doi.org/10.1073/pnas.96.6.2919]
Boehme, D. H., Shotar, A. O. A complex deformity of appendicular skeleton and shoulder with congenital heart disease in three generations of a Jordanian family. Clin. Genet. 36: 442-450, 1989. [PubMed: 2591070] [Full Text: https://doi.org/10.1111/j.1399-0004.1989.tb03374.x]
Borozdin, W., Bravo-Ferrer Acosta, A. M., Seemanova, E., Leipoldt, M., Bamshad, M. J., Unger, S., Kohlhase, J. Contiguous hemizygous deletion of TBX5, TBX3, and RBM19 resulting in a combined phenotype of Holt-Oram and ulnar-mammary syndromes. Am. J. Med. Genet. 140A: 1880-1886, 2006. [PubMed: 16892408] [Full Text: https://doi.org/10.1002/ajmg.a.31340]
Braulke, I., Herzog, S., Thies, U., Zoll, B. Holt-Oram syndrome in four half-siblings with unaffected parents: brief clinical report. Clin. Genet. 39: 241-244, 1991. [PubMed: 2070544] [Full Text: https://doi.org/10.1111/j.1399-0004.1991.tb03021.x]
Brons, J. T. J., Van Geijn, H. P., Wladimiroff, J. W., Van der Harten, J. J., Kwee, M. L., Sobotka-Plojhar, M., Arts, N. F. T. Prenatal ultrasound diagnosis of the Holt-Oram syndrome. Prenatal Diag. 8: 175-181, 1988. [PubMed: 3287365] [Full Text: https://doi.org/10.1002/pd.1970080303]
Davies, P. Obituary: S. Oram, MD, FRCP. Brit. Med. J. 304: 500 only, 1992.
Emerit, I., de Grouchy, J., Laval-Jeantet, M., Corone, P., Vernant, P. Malformations complexes des membres superieurs associees a une cardiopathie congenitale. A propos de six observations. Acta Genet. Med. Gemellol. 14: 132-163, 1965. [PubMed: 14346078]
Fryns, J. P., Bonnet, D., De Smet, L. Holt-Oram syndrome with associated postaxial and central polysyndactyly: further evidence for genetic heterogeneity in the Holt-Oram syndrome. (Letter) Genet. Counsel. 7: 323-324, 1996. [PubMed: 8985738]
Gall, J. C., Jr., Stern, A. M., Cohen, M. M., Adams, M. S., Davidson, R. T. Holt-Oram syndrome: clinical and genetic study of a large family. Am. J. Hum. Genet. 18: 187-200, 1966. [PubMed: 5904863]
Gladstone, I., Jr., Sybert, V. P. Holt-Oram syndrome: penetrance of the gene and lack of maternal effect. Clin. Genet. 21: 98-103, 1982. [PubMed: 7083616] [Full Text: https://doi.org/10.1111/j.1399-0004.1982.tb00743.x]
Glauser, T. A., Zackai, E., Weinberg, P., Clancy, R. Holt-Oram syndrome associated with the hypoplastic left heart syndrome. Clin. Genet. 36: 69-72, 1989. [PubMed: 2766565] [Full Text: https://doi.org/10.1111/j.1399-0004.1989.tb03369.x]
Gruenauer-Kloevekorn, C., Froster, U. G. Holt-Oram syndrome: a new mutation in the TBX5 gene in two unrelated families. Ann. Genet. 46: 19-23, 2003. [PubMed: 12818525] [Full Text: https://doi.org/10.1016/s0003-3995(03)00006-6]
Harris, L. C., Osborne, W. P. Congenital absence or hypoplasia of the radius with ventricular septal defect: ventriculo-radial dysplasia. J. Pediat. 68: 265-272, 1966.
Holt, M., Oram, S. Familial heart disease with skeletal malformations. Brit. Heart J. 22: 236-242, 1960. [PubMed: 14402857] [Full Text: https://doi.org/10.1136/hrt.22.2.236]
Hurst, J. A., Hall, C. M., Baraitser, M. The Holt-Oram syndrome. J. Med. Genet. 28: 406-410, 1991. [PubMed: 1870097] [Full Text: https://doi.org/10.1136/jmg.28.6.406]
Kantaputra, P. N., Yamasaki, K., Ishida, T., Kishino, T., Niikawa, N. A dominantly inherited malformation syndrome with short stature, upper limb anomaly, minor craniofacial anomalies, and absence of TBX5 mutations: report of a Thai family. Am. J. Med. Genet. 111: 301-306, 2002. [PubMed: 12210327] [Full Text: https://doi.org/10.1002/ajmg.10596]
Kristoffersson, U., Mineur, A., Heim, S., Mandahl, N., Mitelman, F. Normal high-resolution karyotypes in three patients with the Holt-Oram syndrome. (Letter) Am. J. Med. Genet. 28: 229-231, 1987. [PubMed: 3674114] [Full Text: https://doi.org/10.1002/ajmg.1320280135]
Kuhn, E., Schaaf, J., Wagner, A. Primary pulmonary hypertension, congenital heart disease and skeletal anomalies in three generations. Jpn. Heart J. 4: 205-223, 1963.
Lenz, W. Personal Communication. Munster, Germany 5/1968.
Letts, R. M., Chudley, A. E., Cumming, G., Shokeir, M. H. The upper limb-cardiovascular syndrome (Holt-Oram syndrome). Clin. Orthop. Relat. Res. 116: 149-154, 1976. [PubMed: 1277635]
Lewis, K. B., Bruce, R. A., Baum, D., Motulsky, A. G. The upper limb-cardiovascular syndrome. An autosomal dominant genetic effect on embryogenesis. JAMA 193: 1080-1086, 1965. [PubMed: 5896868]
Li, Q. Y., Newbury-Ecob, R. A., Terrett, J. A., Wilson, D. I., Curtis, A. R. J., Yi, C. H., Gebuhr, T., Bullen, P. J., Robson, S. C., Strachan, T., Bonnet, D., Lyonnet, S., Young, I. D., Raeburn, J. A., Buckler, A. J., Law, D. J., Brook, J. D. Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. Nature Genet. 15: 21-29, 1997. [PubMed: 8988164] [Full Text: https://doi.org/10.1038/ng0197-21]
Mcfarland, J. C., Fallon, J. T. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 51-1980. New Eng. J. Med. 303: 1519-1526, 1980. [PubMed: 7432422] [Full Text: https://doi.org/10.1056/NEJM198012253032608]
McKusick, V. A. Medical genetics 1960. J. Chronic Dis. 14: 1-198, 1961. Fig. 45.
McKusick, V. A. Personal Communication. Baltimore, Md. 1966.
Moens, P., De Smet, L., Fabry, G., Fryns, J. P. Holt-Oram syndrome: postaxial and central polydactyly as variable manifestation in a four generation family. Genet. Counsel. 4: 277-280, 1993. [PubMed: 8110414]
Newbury-Ecob, R. A., Leanage, R., Raeburn, J. A., Young, I. D. Holt-Oram syndrome: a clinical genetic study. J. Med. Genet. 33: 300-307, 1996. [PubMed: 8730285] [Full Text: https://doi.org/10.1136/jmg.33.4.300]
Ockey, C. H., Feldman, G. V., MacAulay, M. E., Delaney, M. J. A large deletion of the long arm of chromosome no. 4 in a child with limb abnormalities. Arch. Dis. Child. 42: 428-434, 1967. [PubMed: 4951642] [Full Text: https://doi.org/10.1136/adc.42.224.428]
Patel, C., Silcock, L., McMullan, D., Brueton, L., Cox, H. TBX5 intragenic duplication: a family with atypical Holt-Oram syndrome phenotype. Europ. J. Hum. Genet. 20: 863-86, 2012. [PubMed: 22333898] [Full Text: https://doi.org/10.1038/ejhg.2012.16]
Poznanski, A. K., Gall, J. C., Jr., Stern, A. M. Skeletal manifestations of the Holt-Oram syndrome. Radiology 94: 45-54, 1970. [PubMed: 5410358] [Full Text: https://doi.org/10.1148/10.1148/94.1.45]
Ruiz, J. C., Legius, E., Cuppens, H., Moens, P., Marynen, P., Cassiman, J.-J. Exclusion of linkage to 14q23-24 in a family with Holt-Oram syndrome. Clin. Genet. 46: 257-259, 1994. [PubMed: 7820941] [Full Text: https://doi.org/10.1111/j.1399-0004.1994.tb04237.x]
Rybak, M., Kozlowski, K., Kleczkowska, A., Lewandowska, J., Sokolowski, J., Soltysik-Wilk, E. Holt-Oram syndrome associated with ectromelia and chromosomal aberrations. Am. J. Dis. Child. 121: 490-495, 1971. [PubMed: 5581016] [Full Text: https://doi.org/10.1001/archpedi.1971.02100170072008]
Rybak, M. Personal Communication. Krakow, Poland 9/7/1981.
Sahn, D. J., Goldberg, S. J., Allen, H. D., Canale, J. M. Cross-sectional echocardiographic imaging of supracardiac total anomalous pulmonary venous drainage to a vertical vein in a patient with Holt-Oram syndrome. Chest 79: 113-115, 1981. [PubMed: 7449488] [Full Text: https://doi.org/10.1378/chest.79.1.113]
Sletten, L. J., Pierpont, M. E. M. Variation in severity of cardiac disease in Holt-Oram syndrome. Am. J. Med. Genet. 65: 128-132, 1996. [PubMed: 8911604] [Full Text: https://doi.org/10.1002/(SICI)1096-8628(19961016)65:23.0.CO;2-O]
Smith, A. T., Sack, G. H., Jr., Taylor, G. J. Holt-Oram syndrome. J. Pediat. 95: 538-543, 1979. [PubMed: 480027] [Full Text: https://doi.org/10.1016/s0022-3476(79)80758-1]
Temtamy, S. A., McKusick, V. A. The Genetics of Hand Malformations. New York: Alan R. Liss (pub.) 1978. Pp. 117-133.
Terrett, J. A., Newbury-Ecob, R., Cross, G. S., Fenton, I., Raeburn, J. A., Young, I. D., Brook, J. D. Holt-Oram syndrome is a genetically heterogeneous disease with one locus mapping to human chromosome 12q. Nature Genet. 6: 401-404, 1994. [PubMed: 8054982] [Full Text: https://doi.org/10.1038/ng0494-401]
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Contributors:

Marla J. F. O’Neill – updated : 10/18/2006
Carol A. Bocchini – updated : 9/14/2006
Victor A. McKusick – updated : 9/24/2002
Sonja A. Rasmussen – updated : 7/13/2000
Victor A. McKusick – updated : 4/16/1999
Victor A. McKusick – updated : 2/7/1997
Iosif W. Lurie – updated : 1/14/1997
Iosif W. Lurie – updated : 9/7/1996
Iosif W. Lurie – updated : 6/26/1996

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Oram növünü necə bilirəm

▼ TEXT

▼ Description

▼ Clinical Features

▼ Diagnosis

▼ Cytogenetics

▼ Mapping

▼ Inheritance

▼ Molecular Genetics

▼ Nomenclature

▼ History

▼ See Also:

▼ REFERENCES

# 142900

HOLT-ORAM SYNDROME; HOS

HOS1 HEART-HAND SYNDROME ATRIODIGITAL DYSPLASIA

Phenotype-Gene Relationships

TEXT

Description

Clinical Features

Diagnosis

Cytogenetics

Mapping

Inheritance

Molecular Genetics

Nomenclature

History

See Also:

REFERENCES

Related posts:

HOS1
HEART-HAND SYNDROME
ATRIODIGITAL DYSPLASIA