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GENATLAS PHENOTYPE
last update : 22-12-2009
Symbol HOS1
Location 12q24.21
Name Holt-Oram syndrome 1
Other name(s)
  • heart-hand syndrome
  • atriodigital dysplasia
  • Corresponding gene TBX5
    Other symbol(s) HOS
    Main clinical features
  • characterized by radial hypoplasia and cardiac abnormalities, created by null mutations, a predominance of cardiac defect with minimal skeletal malformation in case of missence mutation(s) in the N terminal of the T box and the reverse in missense mutation(s) in the C terminal of the T box
  • Genetic determination autosomal dominant
    Prevalence 1/100000
    Related entries including cases of isolated cardiac malformations
    Function/system disorder cardiovascular
    congenital malformation
    limbs
    Type disease
    Gene product
    Name T-box 5
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    various types   truncated protein causing HOS through the loss of its transactivating domain and/or the nuclear localization signal
    Remark(s) . the most severe TBX5 mutation, G80R, with complete penetrance of the cardiac phenotype, strongly affects pre-mRNA splicing, whereas other mutations with incomplete penetrance of the cardiac phenotype, including R237Q, do not alter the splicing activity of TBX5 (PMID: 19648116))
  • .G125R TBX5 mutation results in a gain-of-function, associated with atypical forms presenting with paroxysmal atrial fibrillation (PMID: 18451335))