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 "first time" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

adrenomyeloneuropathy

alpha-thalassemia

aniridia

aromatase deficiency

canavan disease

carcinoma of the gallbladder

cholangiocarcinoma

classical phenylketonuria

congenital adrenal hyperplasia

congenital toxoplasmosis

cowden syndrome

cushing syndrome

cutaneous mastocytosis

dedifferentiated liposarcoma

dentin dysplasia

dentinogenesis imperfecta

dracunculiasis

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

fabry disease

familial mediterranean fever

gm1 gangliosidosis

harlequin ichthyosis

heparin-induced thrombocytopenia

hirschsprung disease

hodgkin lymphoma, classical

holt-oram syndrome

hydrocephalus with stenosis of the aqueduct of sylvius

junctional epidermolysis bullosa

kabuki syndrome

kallmann syndrome

liposarcoma

locked-in syndrome

lymphangioleiomyomatosis

malignant atrophic papulosis

megacystis-microcolon-intestinal hypoperistalsis syndrome

monosomy 21

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

omenn syndrome

oral submucous fibrosis

papillon-lefèvre syndrome

pendred syndrome

phenylketonuria

primary effusion lymphoma

primary hyperoxaluria type 1

severe combined immunodeficiency

sneddon syndrome

triple a syndrome

trochlear dysplasia

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

werner syndrome

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

zellweger syndrome

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