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Hypoplastic Left Heart Syndrome: Molecular Consequences of Transcription Factor Mutations
Author(s) -
Shay Ashley Elizabeth,
Kirwin Susan,
Prospero Carol,
Pizarro Christian,
Funanage Vicky
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.928.2
Subject(s) - hypoplastic left heart syndrome , medicine , cardiology , ductus arteriosus , hypoplasia , ventricle , bicuspid aortic valve , genetics , aorta , biology , heart disease
Hypoplastic left heart syndrome (HLHS; OMIM #241550) is characterized by abnormal hypoplasia of the left ventricle and aorta, stenosis or atresia of the aortic arch and mitral valve, an atrial septal defect, and a patent ductus arteriosus. The incidence of this rare disorder is about 1 in every 5,000 live births. These abnormalities lead to a decrease in proper blood flow from the left ventricle to the systemic circulatory system. Failure of the systemic circulation leads to profound cyanosis in patients. Without intervention, this condition is fatal within the first days of life. Studies have indicated that HLHS has a strong genetic basis when compared to other congenital heart defects. We are examining the role of several genes associated with cardiac development by screening exons and partial intronic regions for mutations by direct screening of genomic DNA from HLHS patients. Candidate genes for this study include TBX5 , NKX2.5 , GATA4, and GJA1 due to the correlation between mutations in these genes and cardiac defects. These results will be compared within a cohort of HLHS patients to determine if there is a genetic basis for their abnormal cardiovascular development. We have identified three mutations in exon 8 of TBX5 : Val263Met, Ser276Asn, and Arg279Gln, as well as three variations within intronic regions: c. 148‐19 A/T (Intron 2), c.755‐29 C/T (Intron 7), and c.983‐8 C/T (Intron 8). Funding: Nemours Research Programs and NIH‐INBRE (Delaware)