HOS
MCID: HLT001
MIFTS: 66

Holt-Oram Syndrome (HOS)

Categories: Bone diseases, Cardiovascular diseases, Fetal diseases, Genetic diseases, Muscle diseases, Rare diseases

Aliases & Classifications for Holt-Oram Syndrome

MalaCards integrated aliases for Holt-Oram Syndrome:

Name: Holt-Oram Syndrome 57 12 73 25 20 43 58 72 36 29 13 54 6 44 15 39 70
Hos 57 20 43 58 72 17
Atriodigital Dysplasia 57 12 20 43 58
Heart-Hand Syndrome 57 12 20 58
Heart-Hand Syndrome, Type 1 20 43
Ventriculo-Radial Syndrome 20 43
Atrio-Digital Syndrome 12 43
Cardiac-Limb Syndrome 20 43
Atriodigital Dysplasia Type 1 58
Heart-Hand Syndrome Type 1 58
Atrio Digital Syndrome 20
Heart Hand Syndrome 25
Holt Oram Syndrome 54
Hos 1 20
Hos1 57

Characteristics:

Orphanet epidemiological data:

58
holt-oram syndrome
Inheritance: Autosomal dominant; Prevalence: 1-9/1000000 (Europe),1-9/1000000 (Hungary); Age of onset: Neonatal; Age of death: any age;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant


HPO:

31
holt-oram syndrome:
Inheritance autosomal dominant inheritance


GeneReviews:

25
Penetrance The upper-limb malformations in hos are fully penetrant....

Classifications:

Orphanet: 58  
Rare cardiac malformations
Rare bone diseases
Developmental anomalies during embryogenesis


Summaries for Holt-Oram Syndrome

MedlinePlus Genetics : 43 Holt-Oram syndrome is characterized by skeletal abnormalities of the hands and arms (upper limbs) and heart problems.People with Holt-Oram syndrome have abnormally developed bones in their upper limbs. At least one abnormality in the bones of the wrist (carpal bones) is present in affected individuals. Often, these wrist bone abnormalities can be detected only by x-ray. Individuals with Holt-Oram syndrome may have additional bone abnormalities including a missing thumb, a long thumb that looks like a finger, partial or complete absence of bones in the forearm, an underdeveloped bone of the upper arm, and abnormalities of the collar bone or shoulder blades. These skeletal abnormalities may affect one or both of the upper limbs. If both upper limbs are affected, the bone abnormalities can be the same or different on each side. In cases where the skeletal abnormalities are not the same on both sides of the body, the left side is usually more severely affected than the right side.About 75 percent of individuals with Holt-Oram syndrome have heart (cardiac) problems, which can be life-threatening. The most common problem is a defect in the muscular wall (septum) that separates the right and left sides of the heart. A hole in the septum between the upper chambers of the heart (atria) is called an atrial septal defect (ASD), and a hole in the septum between the lower chambers of the heart (ventricles) is called a ventricular septal defect (VSD). Some people with Holt-Oram syndrome have cardiac conduction disease, which is caused by abnormalities in the electrical system that coordinates contractions of the heart chambers. Cardiac conduction disease can lead to problems such as a slower-than-normal heart rate (bradycardia) or a rapid and uncoordinated contraction of the heart muscle (fibrillation). Cardiac conduction disease can occur along with other heart defects (such as ASD or VSD) or as the only heart problem in people with Holt-Oram syndrome.The features of Holt-Oram syndrome are similar to those of a condition called Duane-radial ray syndrome; however, these two disorders are caused by mutations in different genes.

MalaCards based summary : Holt-Oram Syndrome, also known as hos, is related to ventricular septal defect and aortic valve disease 2. An important gene associated with Holt-Oram Syndrome is TBX5 (T-Box Transcription Factor 5), and among its related pathways/superpathways are Cardiac conduction and Human Embryonic Stem Cell Pluripotency. The drugs Pharmaceutical Solutions and Nitroglycerin have been mentioned in the context of this disorder. Affiliated tissues include heart, upper limb and bone, and related phenotypes are joint stiffness and split hand

Disease Ontology : 12 A syndrome characterized by congenital anomalies located in heart and located in upper limb.

GARD : 20 Holt-Oram syndrome affects the bones of the hands and arms and may also affect the heart. People with Holt-Oram syndrome have at least one bone in the wrist that did not form (develop) normally. Other bones in the hands, arms, and shoulder may also have developed abnormally. Many of these developmental changes in the bones can only be seen on an x-ray. Most people with Holt-Oram syndrome also have heart problems, including problems due to the way the heart formed ( congenital ) or problems with the way the heart beats. Holt-Oram syndrome is caused by genetic changes (pathogenic variants or mutations ) in the TBX5 gene. The syndrome is inherited in an autosomal dominant manner. A diagnosis of Holt-Oram syndrome may be suspected when a person has symptoms of the syndrome. An x-ray of the hands, wrists, and arms, echocardiogram of the heart, and genetic testing may be used to confirm the diagnosis. Treatment options for Holt-Oram syndrome may include surgeries to treat bone or heart problems, as well as physical therapy.

OMIM® : 57 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). (142900) (Updated 20-May-2021)

KEGG : 36 Holt-Oram syndrome (HOS) is an autosomal-dominant disorder characterized by bilateral forelimb anomalies and congenital heart diseases. All patients with HOS have abnormal carpal bones and about 85% to 95% develop cardiac malformation including atrial septal defect and ventricular septal defect. The disease is caused by mutations of the T-box transcription factor TBX5.

UniProtKB/Swiss-Prot : 72 Holt-Oram syndrome: Developmental disorder affecting the heart and upper limbs. It is characterized by thumb anomaly and atrial septal defects.

Wikipedia : 73 Holt-Oram syndrome (also called atrio-digital syndrome, atriodigital dysplasia, cardiac-limb syndrome,... more...

GeneReviews: NBK1111

Related Diseases for Holt-Oram Syndrome

Diseases related to Holt-Oram Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 172)
# Related Disease Score Top Affiliating Genes
1 ventricular septal defect 32.2 TBX5 SALL4 NPPA NKX2-5 MYH7 GATA4
2 aortic valve disease 2 31.1 TBX5 NPPA NKX2-5 MYH7 MYH6 GATA4
3 atrioventricular block 31.0 TBX5 NKX2-5 MYH7 GJA5 GATA4
4 patent ductus arteriosus 1 30.9 TBX5 TBX20 TBX1 NKX2-5 MYH6 GATA4
5 thumb deformity 30.8 TBX5 EP300
6 heart septal defect 30.8 TBX5 TBX3 TBX20 TBX2 TBX18 TBX1
7 atrial fibrillation 30.7 TBX5 NPPA MYH7 GJA5
8 sick sinus syndrome 30.6 TBX3 NPPA MYH6 GJA5
9 tricuspid atresia 30.6 TBX5 TBX20 TBX1 NKX2-5 GATA4
10 atrial heart septal defect 30.6 TBX5 TBX3 TBX20 TBX2 TBX18 TBX1
11 mitral valve disease 30.6 TGFB2 NPPA MYH6
12 interatrial communication 30.4 TBX5 TBX20 NKX2-5 MYH6 GATA4
13 atrioventricular septal defect 30.3 TBX5 TBX20 TBX2 TBX1 NKX2-5 MYH6
14 sinoatrial node disease 30.3 TBX5 TBX3 TBX18 NKX2-5 MYH6 GJA5
15 heart disease 30.2 TBX5 TBX4 TBX20 TBX2 TBX1 NPPA
16 left ventricular noncompaction 30.1 TBX5 TBX20 NKX2-5 MYH7 MYH6 GJA5
17 hypertrophic cardiomyopathy 30.0 TGFB2 NPPA NKX2-5 MYH7 MYH6 GJA5
18 tetralogy of fallot 30.0 TBX5 TBX3 TBX20 TBX2 TBX18 TBX1
19 hypoplastic left heart syndrome 30.0 TBX5 TBX4 TBX20 TBX2 TBX1 NPPA
20 brugada syndrome 29.9 TBX5 TBX3 NKX2-5 MYH7 MYH6 GJA5
21 double outlet right ventricle 29.8 TGFB2 TBX5 TBX3 TBX20 TBX2 TBX18
22 dilated cardiomyopathy 29.7 TGFB2 TBX5 TBX20 SRSF2 NPPA NKX2-5
23 patent foramen ovale 29.2 TBX5 TBX3 TBX20 TBX2 TBX1 NPPA
24 ulnar-mammary syndrome 29.2 TBX5 TBX4 TBX3 TBX20 TBX2 TBX18
25 heart-hand syndrome, slovenian type 11.8
26 heart-hand syndrome, spanish type 11.7
27 duane-radial ray syndrome 11.5
28 tabatznik syndrome 11.3
29 polydactyly, preaxial ii 11.3
30 long-thumb brachydactyly syndrome 11.0
31 phocomelia 10.6
32 polydactyly 10.5
33 ovarian primitive germ cell tumor 10.4 SALL4 NKX2-5
34 ovarian endodermal sinus tumor 10.4 SALL4 NKX2-5
35 atrial septal defect ostium primum 10.3
36 central polydactyly 10.3
37 hypoplastic right heart syndrome 10.3 TBX5 TBX20 NKX2-5
38 exudative vitreoretinopathy 7 10.3 TBX5 TBX4
39 mixed germ cell-sex cord neoplasm 10.3 SALL4 GATA4
40 total anomalous pulmonary venous return 1 10.3 TBX5 NKX2-5 GATA4
41 pulmonary valve disease 10.3 TBX5 NKX2-5 GATA4
42 vertebral anomalies and variable endocrine and t-cell dysfunction 10.3 TBX2 TBX1
43 myasthenic syndrome, congenital, 20, presynaptic 10.3 NKX2-5 MYH6
44 germ cell and embryonal cancer 10.3 SALL4 NKX2-5 GATA4
45 patau syndrome 10.3 TBX1 SRSF2 GATA4
46 chromosome 16p13.3 deletion syndrome, proximal 10.3 KAT2B H4C1 EP300
47 hypoplastic left heart syndrome 1 10.3 TBX4 TBX20
48 hypertelorism 10.3
49 renal hypodysplasia/aplasia 1 10.3
50 thrombocytopenia-absent radius syndrome 10.3

Graphical network of the top 20 diseases related to Holt-Oram Syndrome:



Diseases related to Holt-Oram Syndrome

Symptoms & Phenotypes for Holt-Oram Syndrome

Human phenotypes related to Holt-Oram Syndrome:

58 31 (show all 47)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 joint stiffness 58 31 hallmark (90%) Very frequent (99-80%) HP:0001387
2 split hand 58 31 hallmark (90%) Very frequent (99-80%) HP:0001171
3 abnormal clavicle morphology 31 hallmark (90%) HP:0000889
4 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
5 kyphosis 58 31 frequent (33%) Frequent (79-30%) HP:0002808
6 atrial septal defect 58 31 frequent (33%) Frequent (79-30%) HP:0001631
7 ventricular septal defect 58 31 very rare (1%) Frequent (79-30%) HP:0001629
8 abnormality of the metacarpal bones 58 31 frequent (33%) Frequent (79-30%) HP:0001163
9 triphalangeal thumb 58 31 very rare (1%) Frequent (79-30%) HP:0001199
10 aplasia/hypoplasia of the radius 58 31 frequent (33%) Frequent (79-30%) HP:0006501
11 paroxysmal atrial fibrillation 58 31 frequent (33%) Frequent (79-30%) HP:0004757
12 absent thumb 58 31 very rare (1%) Frequent (79-30%) HP:0009777
13 first degree atrioventricular block 58 31 frequent (33%) Frequent (79-30%) HP:0011705
14 broad thumb 58 31 occasional (7.5%) Occasional (29-5%) HP:0011304
15 pectus excavatum 58 31 very rare (1%) Occasional (29-5%) HP:0000767
16 hypoplastic left heart 58 31 occasional (7.5%) Occasional (29-5%) HP:0004383
17 sprengel anomaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000912
18 patent ductus arteriosus 58 31 very rare (1%) Occasional (29-5%) HP:0001643
19 abnormality of the ribs 58 31 occasional (7.5%) Occasional (29-5%) HP:0000772
20 radioulnar synostosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002974
21 down-sloping shoulders 58 31 occasional (7.5%) Occasional (29-5%) HP:0200021
22 finger syndactyly 58 31 occasional (7.5%) Occasional (29-5%) HP:0006101
23 atrioventricular canal defect 58 31 occasional (7.5%) Occasional (29-5%) HP:0006695
24 abnormal aortic morphology 58 31 occasional (7.5%) Occasional (29-5%) HP:0001679
25 phocomelia 58 31 occasional (7.5%) Occasional (29-5%) HP:0009829
26 abnormality of the humerus 58 31 occasional (7.5%) Occasional (29-5%) HP:0003063
27 anomalous pulmonary venous return 58 31 occasional (7.5%) Occasional (29-5%) HP:0010772
28 hypoplasia of the ulna 31 very rare (1%) HP:0003022
29 hypoplasia of the radius 31 very rare (1%) HP:0002984
30 short clavicles 31 very rare (1%) HP:0000894
31 aplasia of the pectoralis major muscle 31 very rare (1%) HP:0009751
32 absent radius 31 very rare (1%) HP:0003974
33 short humerus 31 very rare (1%) HP:0005792
34 secundum atrial septal defect 31 very rare (1%) HP:0001684
35 finger clinodactyly 31 very rare (1%) HP:0040019
36 limited elbow extension 31 very rare (1%) HP:0001377
37 syndactyly 31 very rare (1%) HP:0001159
38 small thenar eminence 31 very rare (1%) HP:0001245
39 short digit 31 very rare (1%) HP:0011927
40 aplasia of the ulna 31 very rare (1%) HP:0003982
41 abnormal vertebral morphology 31 HP:0003468
42 atrioventricular block 58 Frequent (79-30%)
43 abnormality of the clavicle 58 Very frequent (99-80%)
44 partial duplication of thumb phalanx 31 HP:0009944
45 abnormality of cardiovascular system morphology 58 Very frequent (99-80%)
46 abnormality of the carpal bones 31 HP:0001191
47 thoracic scoliosis 31 HP:0002943

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Cardiovascular Vascular:
patent ductus arteriosus

Skeletal Limbs:
triphalangeal thumb
absent thumb
bifid thumb
carpal bone anomalies
upper extremity phocomelia
more
Chest External Features:
absent pectoralis major muscle

Cardiovascular Heart:
ventricular septal defect
hypoplastic left heart syndrome
atrial septal defect (ostium secundum type)

Skeletal Spine:
thoracic scoliosis
vertebral anomalies

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum or carinatum

Clinical features from OMIM®:

142900 (Updated 20-May-2021)

MGI Mouse Phenotypes related to Holt-Oram Syndrome:

46 (show all 13)
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.45 EP300 GATA4 GJA5 MYH6 MYH7 NKX2-5
2 homeostasis/metabolism MP:0005376 10.31 EP300 GATA4 GJA5 KAT2B MYH6 MYH7
3 growth/size/body region MP:0005378 10.28 EP300 GATA4 KAT2B MYH6 NKX2-5 SALL4
4 embryo MP:0005380 10.27 EP300 GATA4 KAT2B NKX2-5 SALL4 TBX1
5 cellular MP:0005384 10.25 EP300 GATA4 MYH6 NKX2-5 SALL4 SRSF2
6 mortality/aging MP:0010768 10.25 EP300 GATA4 GJA5 KAT2B MYH6 MYH7
7 craniofacial MP:0005382 10.15 EP300 NKX2-5 SALL4 TBX1 TBX18 TBX2
8 digestive/alimentary MP:0005381 10.13 EP300 GATA4 GJA5 NKX2-5 SALL4 TBX1
9 muscle MP:0005369 10.1 EP300 GATA4 GJA5 MYH6 MYH7 NKX2-5
10 limbs/digits/tail MP:0005371 9.97 GATA4 SALL4 TBX1 TBX2 TBX3 TBX4
11 normal MP:0002873 9.73 EP300 GATA4 GJA5 KAT2B MYH7 NKX2-5
12 no phenotypic analysis MP:0003012 9.7 GATA4 GJA5 MYH7 NKX2-5 TBX18 TBX20
13 respiratory system MP:0005388 9.23 EP300 GATA4 GJA5 MYH6 NKX2-5 TBX1

Drugs & Therapeutics for Holt-Oram Syndrome

Drugs for Holt-Oram Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 15)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Pharmaceutical Solutions Phase 3
2
Nitroglycerin Approved, Investigational Phase 1 55-63-0 4510
3
Curcumin Approved, Experimental, Investigational Phase 1 458-37-7 969516
4 Anti-Inflammatory Agents Phase 1
5 Antirheumatic Agents Phase 1
6 Anti-Inflammatory Agents, Non-Steroidal Phase 1
7 Analgesics Phase 1
8 Analgesics, Non-Narcotic Phase 1
9
Carbon monoxide Approved, Investigational 630-08-0 281
10
Hydroxyurea Approved 127-07-1 3657
11
Resveratrol Investigational 501-36-0 445154
12 Antioxidants
13 Protective Agents
14 Platelet Aggregation Inhibitors
15 Vaccines

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Randomised Placebo-Controlled Trial to Investigate the Effect of Pre-treatment With Haem Arginate (Normosang) on Heme-Oxygenase 1 (HO-1) Upregulation in Recipients of Deceased Donor Kidneys Completed NCT01430156 Phase 3 Heme arginate (Normosang);0.9% sodium chloride
2 Pilot Trial: The Effects of Intravenous Heme Arginate on HO-1 Expression and Oxidative Stress in the Human Heart Completed NCT02314780 Phase 2 Heme arginate 3mg/kg;Heme arginate 1mg/kg;Placebo
3 Dose Escalation, Randomized, Placebo Controlled Study to Investigate the Effects of Intravenous Heme Arginate on Heme Oxygenase-1 (HO-1) and Heme Metabolism in Association With HO-1 Gene GTn Promoter Polymorphism in Healthy Male Subjects Completed NCT00682370 Phase 1 saline solution;heme arginate;heme arginate;heme arginate
4 The Effects of Oral Curcumin on Heme Oxygenase-1 (HO-1) in Healthy Male Subjects Completed NCT00895167 Phase 1
5 Analysis of Anti-inflammatory and Antioxidant Pathways in Lung Diseases by Haem Oxygenase-1 (HO-1) in Induced Sputum and Carbon Monoxide (CO) in Exhaled Air Unknown status NCT01140685
6 The Effects of the Dietary Supplement Trans-resveratrol on Heme Oxygenase-1 (HO-1) and Sirtuins Expression in PBMCs in Healthy Male Subjects: A Pilot Study. Completed NCT01768507
7 Monocytic Expression of Heme Oxidase-1 (HO-1) in Sickle Cell Patients and Correlation With the Humoral Immune Response to Vaccine and With Allo-immunization Completed NCT03111589

Search NIH Clinical Center for Holt-Oram Syndrome

Cochrane evidence based reviews: holt-oram syndrome

Genetic Tests for Holt-Oram Syndrome

Genetic tests related to Holt-Oram Syndrome:

# Genetic test Affiliating Genes
1 Holt-Oram Syndrome 29 TBX5

Anatomical Context for Holt-Oram Syndrome

The Foundational Model of Anatomy Ontology organs/tissues related to Holt-Oram Syndrome:

19
Heart, Upper Limb

MalaCards organs/tissues related to Holt-Oram Syndrome:

40
Heart, Bone, Pituitary, Eye, Retina, Kidney, Uterus

Publications for Holt-Oram Syndrome

Articles related to Holt-Oram Syndrome:

(show top 50) (show all 453)
# Title Authors PMID Year
1
Three novel TBX5 mutations in Chinese patients with Holt-Oram syndrome. 61 57 6 25 54
10842287 2000
2
Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations. 61 54 57 25 6
10077612 1999
3
Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. 61 25 6 54 57
8988164 1997
4
TBX5 intragenic duplication: a family with an atypical Holt-Oram syndrome phenotype. 61 25 57 6
22333898 2012
5
Holt-Oram syndrome: a new mutation in the TBX5 gene in two unrelated families. 57 54 6 61
12818525 2003
6
Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt-Oram syndrome. 61 54 57 6
8988165 1997
7
Structural basis of TBX5-DNA recognition: the T-box domain in its DNA-bound and -unbound form. 61 6 25
20450920 2010
8
Variation in severity of cardiac disease in Holt-Oram syndrome. 61 57 25
8911604 1996
9
Holt-Oram syndrome: a clinical genetic study. 25 57 61
8730285 1996
10
The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome) 25 57 61
8114858 1994
11
Holt-Oram syndrome in four half-siblings with unaffected parents: brief clinical report. 25 57 61
2070544 1991
12
Skeletal manifestations of the Holt-Oram syndrome. 57 61 25
5410358 1970
13
Functional role of transcriptional factor TBX5 in pre-mRNA splicing and Holt-Oram syndrome via association with SC35. 61 6 54
19648116 2009
14
Holt-Oram syndrome with right lung agenesis caused by a de novo mutation in the TBX5 gene. 54 61 57
17366586 2007
15
Novel TBX5 mutations and molecular mechanism for Holt-Oram syndrome. 6 61 54
12624158 2003
16
Functional analysis of TBX5 missense mutations associated with Holt-Oram syndrome. 61 54 6
12499378 2003
17
A dominantly inherited malformation syndrome with short stature, upper limb anomaly, minor craniofacial anomalies, and absence of TBX5 mutations: report of a Thai family. 61 54 57
12210327 2002
18
Characterization of the TBX5 binding site and analysis of mutations that cause Holt-Oram syndrome. 61 54 6
11555635 2001
19
A complex deformity of appendicular skeleton and shoulder with congenital heart disease in three generations of a Jordanian family. 57 25
2591070 1989
20
Familial heart disease with skeletal malformations. 57 25
14402857 1960
21
Holt-Oram syndrome in two families diagnosed with left ventricular noncompaction and conduction disease. 61 6
29755943 2018
22
Synergistic activation of cardiac genes by myocardin and Tbx5. 61 6
21897873 2011
23
Functional analysis of novel TBX5 T-box mutations associated with Holt-Oram syndrome. 6 61
20519243 2010
24
Tbx5-mediated expression of Ca(2+)/calmodulin-dependent protein kinase II is necessary for zebrafish cardiac and pectoral fin morphogenesis. 54 61 25
19345202 2009
25
Functional analysis of the novel TBX5 c.1333delC mutation resulting in an extended TBX5 protein. 54 61 25
18828908 2008
26
A novel TBX5 missense mutation (V263M) in a family with atrial septal defects and postaxial hexodactyly. 25 61 54
18706711 2008
27
Novel TBX5 mutations in patients with Holt-Oram syndrome. 25 54 61
17534187 2007
28
Expanding the spectrum of TBX5 mutations in Holt-Oram syndrome: detection of two intragenic deletions by quantitative real time PCR, and report of eight novel point mutations. 54 61 25
16917909 2006
29
TBX5 genetic testing validates strict clinical criteria for Holt-Oram syndrome. 25 61 54
16183809 2005
30
Expressivity of Holt-Oram syndrome is not predicted by TBX5 genotype. 54 61 25
12789647 2003
31
Tbx5 is required for forelimb bud formation and continued outgrowth. 61 54 25
12736217 2003
32
Holt-Oram syndrome: is there a "face"? 54 61 25
12687661 2003
33
Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation. 6 61
11431700 2001
34
TBX5 transcription factor regulates cell proliferation during cardiogenesis. 25 54 61
11161571 2001
35
Holt-Oram syndrome with associated postaxial and central polydactyly. Further evidence for genetic heterogeneity in the Holt-Oram syndrome. 57 61
8985738 1996
36
Exclusion of linkage to 14q23-24 in a family with Holt-Oram syndrome. 61 57
7820941 1994
37
Holt-Oram syndrome is a genetically heterogeneous disease with one locus mapping to human chromosome 12q. 61 57
8054982 1994
38
Holt-Oram syndrome: postaxial and central polydactyly as variable manifestations in a four generations family. 57 61
8110414 1993
39
The Holt-Oram syndrome. 61 57
1870097 1991
40
Holt-Oram syndrome associated with the hypoplastic left heart syndrome. 61 57
2766565 1989
41
Prenatal ultrasound diagnosis of the Holt-Oram syndrome. 61 57
3287365 1988
42
Normal high-resolution karyotypes in three patients with the Holt-Oram syndrome. 61 57
3674114 1987
43
Holt-Oram syndrome in China: a collective review of 18 cases. 61 57
3953367 1986
44
Two patients with interstitial del (14q), one with features of Holt-Oram syndrome. Exclusion mapping of PI (alpha-1-antitrypsin). 61 57
6335371 1984
45
Holt-Oram syndrome: penetrance of the gene and lack of maternal effect. 61 57
7083616 1982
46
Holt Oram syndrome mistaken for thalidomide embryopathy--embryological considerations. 61 57
7075631 1982
47
Cross-sectional echocardiographic imaging of supracardiac total anomalous pulmonary venous drainage to a vertical vein in a patient with Holt-Oram syndrome. 61 57
7449488 1981
48
Holt-Oram syndrome. 61 57
480027 1979
49
The upper limb-cardiovascular syndrome, (Holt-Oram syndrome). 61 57
1277635 1976
50
Holt-Oram syndrome associated with ectromelia and chromosomal aberrations. 57 61
5581016 1971

Variations for Holt-Oram Syndrome

ClinVar genetic disease variations for Holt-Oram Syndrome:

6 (show top 50) (show all 299)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TBX5 TBX5, 1491C-T SNV Pathogenic 7991 GRCh37:
GRCh38:
2 TBX5 NM_000192.3(TBX5):c.238G>A (p.Gly80Arg) SNV Pathogenic 7994 rs104894381 GRCh37: 12:114839635-114839635
GRCh38: 12:114401830-114401830
3 TBX5 NM_000192.3(TBX5):c.416del (p.Pro139fs) Deletion Pathogenic 7996 rs1593880204 GRCh37: 12:114836472-114836472
GRCh38: 12:114398667-114398667
4 TBX5 NM_000192.3(TBX5):c.145C>A (p.Gln49Lys) SNV Pathogenic 7997 rs104894383 GRCh37: 12:114841559-114841559
GRCh38: 12:114403754-114403754
5 TBX5 NM_000192.3(TBX5):c.161T>C (p.Ile54Thr) SNV Pathogenic 7998 rs104894384 GRCh37: 12:114839712-114839712
GRCh38: 12:114401907-114401907
6 TBX5 NM_000192.3(TBX5):c.408C>A (p.Tyr136Ter) SNV Pathogenic 7999 rs104894379 GRCh37: 12:114836480-114836480
GRCh38: 12:114398675-114398675
7 TBX5 NM_000192.3(TBX5):c.105del (p.Ser36fs) Deletion Pathogenic 369677 rs1057516042 GRCh37: 12:114841599-114841599
GRCh38: 12:114403794-114403794
8 TGFB2 NM_003238.5(TGFB2):c.252dup (p.Arg85fs) Duplication Pathogenic 408427 rs1553292112 GRCh37: 1:218520293-218520294
GRCh38: 1:218346951-218346952
9 TGFB2 NM_003238.5(TGFB2):c.892_901del (p.Arg298fs) Deletion Pathogenic 459270 rs1553303203 GRCh37: 1:218609449-218609458
GRCh38: 1:218436107-218436116
10 TGFB2 NC_000001.11:g.(?_218346682)_(218441382_?)del Deletion Pathogenic 528890 GRCh37: 1:218520024-218614724
GRCh38: 1:218346682-218441382
11 TBX5 NM_000192.3(TBX5):c.246_249del (p.Met83fs) Deletion Pathogenic 561217 rs1565941587 GRCh37: 12:114837431-114837434
GRCh38: 12:114399626-114399629
12 TBX5 GRCh37/hg19 12q24.21(chr12:114791609-114793234) copy number loss Pathogenic 625740 GRCh37: 12:114791609-114793234
GRCh38:
13 TBX5 NM_000192.3:c.(982+1_983-1)_(*1602_?)del Deletion Pathogenic 633719 GRCh37:
GRCh38:
14 TBX5 NM_000192.3(TBX5):c.1269C>G (p.Tyr423Ter) SNV Pathogenic 633722 rs756049331 GRCh37: 12:114793625-114793625
GRCh38: 12:114355820-114355820
15 TBX5 NM_000192.3(TBX5):c.1303del (p.Leu435fs) Deletion Pathogenic 633723 GRCh37: 12:114793591-114793591
GRCh38: 12:114355786-114355786
16 TBX5 NM_000192.3:c.(362+1_363-1)_(*1602_?)del Deletion Pathogenic 633724 GRCh37:
GRCh38:
17 TBX5 NM_000192.3(TBX5):c.879T>A (p.Cys293Ter) SNV Pathogenic 633725 rs1565927740 GRCh37: 12:114804073-114804073
GRCh38: 12:114366268-114366268
18 TBX5 NM_000192.3(TBX5):c.500del (p.Pro167fs) Deletion Pathogenic 633735 GRCh37: 12:114836388-114836388
GRCh38: 12:114398583-114398583
19 TBX5 NM_000192.3:c.(663+1_664-1)_(755+1_756-1)dup Duplication Pathogenic 633736 GRCh37:
GRCh38:
20 TBX5 NM_000192.3(TBX5):c.1346del (p.Gln449fs) Deletion Pathogenic 633737 GRCh37: 12:114793548-114793548
GRCh38: 12:114355743-114355743
21 TBX5 NM_000192.3(TBX5):c.728_729del (p.Glu243fs) Deletion Pathogenic 633738 GRCh37: 12:114823307-114823308
GRCh38: 12:114385502-114385503
22 TBX5 NM_080717.3(TBX5):c.483_484TA[1] (p.Ile162fs) Microsatellite Pathogenic 633739 GRCh37: 12:114832573-114832574
GRCh38: 12:114394768-114394769
23 TBX5 NM_000192.3:c.(?_-667)_(755+1_756-1)dup Duplication Pathogenic 633740 GRCh37:
GRCh38:
24 TBX5 NM_000192.3(TBX5):c.1203G>A (p.Trp401Ter) SNV Pathogenic 633741 rs377649723 GRCh37: 12:114793691-114793691
GRCh38: 12:114355886-114355886
25 TBX5 NM_000192.3:c.(663+1_664-1)_(755+1_756-1)del Deletion Pathogenic 633742 GRCh37:
GRCh38:
26 TBX5 NM_000192.3(TBX5):c.845C>T (p.Ser282Phe) SNV Pathogenic 633743 rs1565927794 GRCh37: 12:114804107-114804107
GRCh38: 12:114366302-114366302
27 TBX5 NM_000192.3(TBX5):c.680_683del (p.Ile227fs) Deletion Pathogenic 633744 rs1565935410 GRCh37: 12:114823353-114823356
GRCh38: 12:114385548-114385551
28 TBX5 NM_000192.3(TBX5):c.713dup (p.Ser239fs) Duplication Pathogenic 633728 GRCh37: 12:114823322-114823323
GRCh38: 12:114385517-114385518
29 TBX5 NM_000192.3(TBX5):c.1045G>T (p.Glu349Ter) SNV Pathogenic 633729 rs1565923887 GRCh37: 12:114793849-114793849
GRCh38: 12:114356044-114356044
30 TBX5 NM_000192.3(TBX5):c.342C>A (p.Tyr114Ter) SNV Pathogenic 633730 rs1565941422 GRCh37: 12:114837338-114837338
GRCh38: 12:114399533-114399533
31 TBX5 NM_000192.3(TBX5):c.1084C>T (p.Gln362Ter) SNV Pathogenic 633731 rs765204502 GRCh37: 12:114793810-114793810
GRCh38: 12:114356005-114356005
32 TBX5 NM_000192.3(TBX5):c.537C>A (p.Tyr179Ter) SNV Pathogenic 633732 rs1565939337 GRCh37: 12:114832672-114832672
GRCh38: 12:114394867-114394867
33 TBX5 NM_000192.3:c.(?_-38)_(242+1_243-1)dup Duplication Pathogenic 633733 GRCh37:
GRCh38:
34 TBX5 NM_000192.3:c.1033_1034dupGA Duplication Pathogenic 633746 GRCh37:
GRCh38:
35 TBX5 NM_000192.3(TBX5):c.496del (p.Asp166fs) Deletion Pathogenic 633747 GRCh37: 12:114836392-114836392
GRCh38: 12:114398587-114398587
36 TBX5 NM_000192.3:c.67_81delins Indel Pathogenic 633748 GRCh37:
GRCh38:
37 TBX5 NM_000192.3:c.(?_-667)_(*1602_?)del Deletion Pathogenic 633749 GRCh37:
GRCh38:
38 TBX5 NM_000192.3(TBX5):c.426del (p.Ala143fs) Deletion Pathogenic 633750 GRCh37: 12:114836462-114836462
GRCh38: 12:114398657-114398657
39 TBX5 NM_000192.3(TBX5):c.457dup (p.Val153fs) Duplication Pathogenic 633753 GRCh37: 12:114836430-114836431
GRCh38: 12:114398625-114398626
40 TBX5 NM_000192.3(TBX5):c.703G>T (p.Gly235Ter) SNV Pathogenic 633754 rs1565935397 GRCh37: 12:114823333-114823333
GRCh38: 12:114385528-114385528
41 TBX5 NM_000192.3(TBX5):c.295A>T (p.Lys99Ter) SNV Pathogenic 633755 rs1565941529 GRCh37: 12:114837385-114837385
GRCh38: 12:114399580-114399580
42 TBX5 NM_000192.3(TBX5):c.559_572dup (p.Asn191fs) Duplication Pathogenic 633756 rs1565939303 GRCh37: 12:114832636-114832637
GRCh38: 12:114394831-114394832
43 TBX5 NM_000192.3(TBX5):c.119C>A (p.Ser40Ter) SNV Pathogenic 633757 rs903933027 GRCh37: 12:114841585-114841585
GRCh38: 12:114403780-114403780
44 TBX5 NM_000192.3:c.(362+1_363-1)_(510+1_511-1)del Deletion Pathogenic 633758 GRCh37:
GRCh38:
45 TBX5 NM_000192.3(TBX5):c.924del (p.Asn309fs) Deletion Pathogenic 633759 GRCh37: 12:114804028-114804028
GRCh38: 12:114366223-114366223
46 TBX5 NM_000192.3:c.946C>T SNV Pathogenic 633760 GRCh37:
GRCh38:
47 TBX5 NM_000192.3(TBX5):c.73_74insT (p.Asp25fs) Insertion Pathogenic 633768 rs1565943328 GRCh37: 12:114841630-114841631
GRCh38: 12:114403825-114403826
48 TBX5 NM_000192.3(TBX5):c.1074del (p.Pro359fs) Deletion Pathogenic 633769 GRCh37: 12:114793820-114793820
GRCh38: 12:114356015-114356015
49 TBX5 NM_000192.3(TBX5):c.674T>G (p.Leu225Ter) SNV Pathogenic 633770 rs1565935432 GRCh37: 12:114823362-114823362
GRCh38: 12:114385557-114385557
50 TBX5 NM_000192.3(TBX5):c.943C>T (p.Gln315Ter) SNV Pathogenic 633771 rs1565927645 GRCh37: 12:114804009-114804009
GRCh38: 12:114366204-114366204

UniProtKB/Swiss-Prot genetic disease variations for Holt-Oram Syndrome:

72
# Symbol AA change Variation ID SNP ID
1 TBX5 p.Arg237Gln VAR_007456 rs104894378
2 TBX5 p.Gly80Arg VAR_009701 rs104894381
3 TBX5 p.Arg237Trp VAR_009702 rs104894382
4 TBX5 p.Gln49Lys VAR_015381 rs104894383
5 TBX5 p.Ile54Thr VAR_015382 rs104894384

Expression for Holt-Oram Syndrome

Search GEO for disease gene expression data for Holt-Oram Syndrome.

Pathways for Holt-Oram Syndrome

Pathways related to Holt-Oram Syndrome according to GeneCards Suite gene sharing:

(show all 12)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.66 TBX5 NPPA NKX2-5 MYH6 KAT2B GATA4
2
Show member pathways
12.33 TGFB2 TBX5 NPPA NKX2-5 MYH7 GATA4
3
Show member pathways
12.31 NPPA MYH7 MYH6 GATA4
4
Show member pathways
11.99 TBX5 NPPA NKX2-5 KAT2B GATA4 EP300
5 11.85 MYH7 MYH6 KAT2B GATA4 EP300
6 11.71 TGFB2 TBX5 NKX2-5 GATA4
7 11.56 NKX2-5 KAT2B EP300
8 11.24 KAT2B H4C1 EP300
9 11.08 TBX5 TBX20 NKX2-5 MYH6 GATA4
10 10.8 NPPA NKX2-5 MYH7 GATA4
11 10.76 TBX5 TBX20 TBX2 TBX1 NKX2-5 GATA4
12 10.28 NPPA NKX2-5 GATA4

GO Terms for Holt-Oram Syndrome

Cellular components related to Holt-Oram Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 10.03 TBX5 TBX4 TBX3 TBX20 TBX2 TBX18
2 protein-containing complex GO:0032991 9.5 TBX5 SALL4 NPPA NKX2-5 KAT2B H4C1
3 protein-DNA complex GO:0032993 9.43 TBX5 NKX2-5 EP300
4 myosin filament GO:0032982 9.37 MYH7 MYH6
5 muscle myosin complex GO:0005859 9.32 MYH7 MYH6
6 chromatin GO:0000785 9.28 TBX5 TBX4 TBX3 TBX20 TBX2 TBX18

Biological processes related to Holt-Oram Syndrome according to GeneCards Suite gene sharing:

(show top 50) (show all 54)
# Name GO ID Score Top Affiliating Genes
1 regulation of transcription by RNA polymerase II GO:0006357 10.25 TBX5 TBX4 TBX3 TBX20 TBX2 TBX18
2 regulation of transcription, DNA-templated GO:0006355 10.24 TBX5 TBX4 TBX3 TBX20 TBX2 TBX18
3 multicellular organism development GO:0007275 10.21 TBX5 TBX4 TBX3 TBX20 TBX2 TBX18
4 positive regulation of transcription by RNA polymerase II GO:0045944 10.21 TBX5 TBX20 TBX1 SALL4 NKX2-5 KAT2B
5 negative regulation of transcription by RNA polymerase II GO:0000122 10.19 TBX3 TBX20 TBX2 TBX18 SALL4 NKX2-5
6 positive regulation of transcription, DNA-templated GO:0045893 10.15 TBX5 TBX3 TBX20 TBX1 NKX2-5 KAT2B
7 negative regulation of transcription, DNA-templated GO:0045892 10.11 TBX3 TBX20 TBX2 SRSF2 NKX2-5
8 positive regulation of cell proliferation GO:0008284 10.09 TGFB2 TBX3 TBX2 TBX1 NKX2-5
9 Notch signaling pathway GO:0007219 9.89 TBX2 KAT2B EP300
10 muscle contraction GO:0006936 9.89 TBX20 MYH7 MYH6
11 lung development GO:0030324 9.87 TBX5 TBX4 EP300
12 embryonic limb morphogenesis GO:0030326 9.86 TGFB2 TBX5 TBX4 SALL4
13 regulation of megakaryocyte differentiation GO:0045652 9.85 KAT2B H4C1 EP300
14 heart looping GO:0001947 9.85 TBX3 TBX20 TBX2 NKX2-5 GATA4
15 positive regulation of Notch signaling pathway GO:0045747 9.84 TGFB2 KAT2B EP300
16 ventricular septum development GO:0003281 9.84 TBX5 SALL4 GJA5 GATA4
17 cardiac muscle contraction GO:0060048 9.83 NKX2-5 MYH7 MYH6
18 aortic valve morphogenesis GO:0003180 9.83 TBX20 NPPA NKX2-5 GATA4
19 positive regulation of cardiac muscle cell proliferation GO:0060045 9.82 TBX5 TBX20 TBX2
20 ventricular septum morphogenesis GO:0060412 9.8 TGFB2 TBX3 NKX2-5
21 heart morphogenesis GO:0003007 9.8 TGFB2 TBX3 TBX2 TBX1 NKX2-5
22 cardiac muscle cell differentiation GO:0055007 9.78 TBX5 TBX3 NKX2-5 GATA4
23 endocardial cushion morphogenesis GO:0003203 9.77 TGFB2 TBX20 TBX2
24 smooth muscle cell differentiation GO:0051145 9.77 TBX3 TBX2 TBX18
25 outflow tract morphogenesis GO:0003151 9.77 TBX3 TBX20 TBX2 TBX1 GJA5
26 cardiac right ventricle morphogenesis GO:0003215 9.76 TGFB2 TBX20 GATA4
27 heart development GO:0007507 9.76 TGFB2 TBX5 TBX1 SALL4 NKX2-5 KAT2B
28 cardiac muscle hypertrophy in response to stress GO:0014898 9.75 NPPA MYH7 MYH6
29 adult heart development GO:0007512 9.74 NKX2-5 MYH7 MYH6
30 embryonic heart tube development GO:0035050 9.73 TBX3 TBX20 TBX2 NKX2-5
31 pharyngeal system development GO:0060037 9.72 TBX1 NKX2-5
32 outflow tract septum morphogenesis GO:0003148 9.72 TGFB2 TBX20 TBX2 TBX1 NKX2-5
33 positive regulation of transcription of Notch receptor target GO:0007221 9.71 KAT2B EP300
34 cell growth involved in cardiac muscle cell development GO:0061049 9.71 NPPA GATA4
35 aorta morphogenesis GO:0035909 9.7 TBX2 TBX1
36 striated muscle contraction GO:0006941 9.7 MYH7 MYH6
37 protein acetylation GO:0006473 9.7 KAT2B EP300
38 atrioventricular valve morphogenesis GO:0003181 9.69 TGFB2 TBX5
39 cardiac muscle tissue morphogenesis GO:0055008 9.69 TBX20 NKX2-5
40 endocardial cushion development GO:0003197 9.68 TBX5 GATA4
41 forelimb morphogenesis GO:0035136 9.68 TBX5 TBX3
42 positive regulation of heart contraction GO:0045823 9.68 TGFB2 NKX2-5
43 atrial septum development GO:0003283 9.68 TBX5 GJA5
44 internal peptidyl-lysine acetylation GO:0018393 9.67 KAT2B EP300
45 peptidyl-lysine acetylation GO:0018394 9.67 KAT2B EP300
46 sinoatrial node cell development GO:0060931 9.66 TBX3 TBX18
47 atrial septum primum morphogenesis GO:0003289 9.65 TGFB2 GATA4
48 mammary placode formation GO:0060596 9.64 TBX3 TBX2
49 N-terminal peptidyl-lysine acetylation GO:0018076 9.63 KAT2B EP300
50 ureteric peristalsis GO:0072105 9.62 TBX3 TBX2

Molecular functions related to Holt-Oram Syndrome according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 DNA binding GO:0003677 10.03 TBX5 TBX4 TBX3 TBX20 TBX2 TBX18
2 sequence-specific DNA binding GO:0043565 9.91 TBX5 TBX3 TBX2 TBX1 NKX2-5 GATA4
3 sequence-specific double-stranded DNA binding GO:1990837 9.91 TBX3 TBX20 TBX2 TBX18 TBX1 NKX2-5
4 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000977 9.88 TBX5 TBX20 KAT2B GATA4 EP300
5 transcription factor binding GO:0008134 9.88 TBX5 SALL4 NKX2-5 KAT2B GATA4 EP300
6 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.85 TBX5 TBX4 TBX3 TBX20 TBX2 TBX18
7 RNA polymerase II activating transcription factor binding GO:0001102 9.63 TBX3 TBX20 EP300
8 RNA polymerase II transcription factor binding GO:0001085 9.62 TBX3 TBX20 GATA4 EP300
9 DNA-binding transcription factor activity GO:0003700 9.61 TBX5 TBX4 TBX3 TBX20 TBX2 TBX18
10 bacterial-type RNA polymerase transcriptional activator activity, sequence-specific DNA binding GO:0001216 9.52 NKX2-5 GATA4
11 peptide-lysine-N-acetyltransferase activity GO:0061733 9.51 KAT2B EP300
12 lysine N-acetyltransferase activity, acting on acetyl phosphate as donor GO:0004468 9.49 KAT2B EP300
13 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.36 TBX5 TBX4 TBX3 TBX20 TBX2 TBX18

Sources for Holt-Oram Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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