title: Differential duplication of an intronic region in the NFATC1 gene in patients with congenital heart disease.
abstract: Most forms of congenital heart disease (CHD) result from aberrations in cardiac morphogenesis including errors in septation, valve formation, and proper patterning of the great vessels. Transcription factors are key proteins that dictate mRNA synthesis rate and subsequent protein production in most eukaryotes. NFATC1 belongs to the Rel family of transcription factors. In mice, it is expressed in the embryonic heart and is restricted to the endocardium where it plays a major role in valve formation. To establish a role for NFATC1 in CHD, we started screening for mutations in the exons encoding the DNA-binding domain of NFATC1 in patients enrolled in our study on CHD in Lebanon. DNA was extracted from patients with pulmonary stenosis (PS), tricuspid atresia (TA) and ventricular septal defect (VSD). PCR amplification and DNA sequencing were done on the patients and their parents and (or) siblings. PCR amplification of the exon 7 region showed that 2 bands are obtained in 57% of patients with CHD (32/56) and in 45% of their healthy parents and (or) siblings. Sequencing of the 2 bands revealed that both are amplicons of the exon 7 region, and that the additional band harbors an additional 44 nucleotides segment in the intronic region. The homozygous form of this allele was only present in patients with VSD (2/21). A screen of a pool of 81 healthy, unrelated individuals showed no presence for the homozygous form of this allele, suggesting that NFATC1 is a potential VSD-susceptibility gene.
authors.affiliation: Department of Biochemistry, American University of Beirut (AUB), Bliss St., P.O. Box 110236, Beirut, Lebanon.
authors.forename: Amin
authors.initials: A
authors.lastname: Yehya
authors.forename: Ramzi
authors.initials: R
authors.lastname: Souki
authors.forename: Fadi
authors.initials: F
authors.lastname: Bitar
authors.forename: Georges
authors.initials: G
authors.lastname: Nemer
mesh_terms: D017398:Alternative Splicing; D002648:Child; D005091:Exons; D005260:Female; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease; D006330:Heart Defects, Congenital / Q000235:genetics*; D006345:Heart Septal Defects, Ventricular / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns; D007861:Lebanon; D008297:Male; D050778:NFATC Transcription Factors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000235:genetics; D011666:Pulmonary Valve Stenosis / Q000235:genetics; D020080:Tandem Repeat Sequences; D018785:Tricuspid Atresia / Q000097:blood / Q000235:genetics
chemical_list: D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D020033:Protein Isoforms