TBX5 mutations in non-Holt-Oram syndrome (HOS) malformed hearts.

[holt-oram syndrome]

The T -box transcription factor Tbx 5 is important in mammalian cardiac development . Mutations in the human TBX 5 gene cause Holt-Oram syndrome (HOS ), a disorder characterized by heart and upper limb deformities . To determine the role of TBX 5 in non-HOS patients with complex cardiac malformations , we analyzed 68 explanted hearts from unrelated patients with various cardiac abnormalities including atrial (ASD ), ventricular (VSD ) and atrioventricular septal defects (AVSD ). Direct sequencing detected nine mutations in diseased cardiac tissues of patients , eight of which are novel . Six mutations would affect amino acids in the T -domain , and one (c .236 C >T , p .Ala 79 V al ) is within the recently identified nuclear localization signal (NLS 1 ) region . Further , mutations were found in patients with ASD and AVSD , but not with VSD ; and mutations were absent in normal heart tissue of same patients , thus indicating somatic origin . Our results suggest a possible role of somatically occurring TBX 5 mutations in congenital heart disease . We show for the first time TBX 5 mutations in non-HOS associated cardiac malformations and we identified a novel missense mutation that would impact nuclear localization of TBX 5 .

Diseases
Validation

Diseases presenting "heart disease" symptom

22q11.2 deletion syndrome

achondroplasia

acute rheumatic fever

adrenal incidentaloma

child syndrome

classical phenylketonuria

cohen syndrome

congenital diaphragmatic hernia

dentinogenesis imperfecta

esophageal adenocarcinoma

fabry disease

familial mediterranean fever

heparin-induced thrombocytopenia

hirschsprung disease

holt-oram syndrome

homocystinuria without methylmalonic aciduria

kabuki syndrome

monosomy 21

omenn syndrome

phenylketonuria

sneddon syndrome

systemic capillary leak syndrome

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

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