title: Resequencing the whole MYH7 gene (including the intronic, promoter, and 3' UTR sequences) in hypertrophic cardiomyopathy.
abstract: MYH7 mutations are found in ~20% of hypertrophic cardiomyopathy (HCM) patients. Currently, mutational analysis is based on the sequencing of the coding exons and a few exon-flanking intronic nucleotides, resulting in omission of single-exon deletions and mutations in internal intronic, promoter, and 3' UTR regions. We amplified and sequenced large MYH7 fragments in 60 HCM patients without previously identified sarcomere mutations. Lack of aberrant PCR fragments excluded single-exon deletions in the patients. Instead, we identified several new rare intronic variants. An intron 26 single nucleotide insertion (-5 insC) was predicted to affect pre-mRNA splicing, but allele frequencies did not differ between patients and controls (n = 150). We found several rare promoter variants in the patients compared to controls, some of which were in binding sites for transcription factors and could thus affect gene expression. Only one rare 3' UTR variant (c.*29T>C) found in the patients was absent among the controls. This nucleotide change would not affect the binding of known microRNAs. Therefore, MYH7 mutations outside the coding exon sequences would be rarely found among HCM patients. However, changes in the promoter region could be linked to the risk of developing HCM. Further research to define the functional effect of these variants on gene expression is necessary to confirm the role of the MYH7 promoter in cardiac hypertrophy.
authors: Molecular Genetics-Laboratory of Medicine-Renal Foundation (IRSIN-FRIAT), University Central Hospital Asturias (HUCA), Oviedo, Spain. eliecer.coto@sespa.princast.es
authors: Eliecer
authors: E
authors: Coto
authors: Julián R
authors: JR
authors: Reguero
authors: María
authors: M
authors: Palacín
authors: Juan
authors: J
authors: Gómez
authors: Belén
authors: B
authors: Alonso
authors: Sara
authors: S
authors: Iglesias
authors: María
authors: M
authors: Martín
authors: Beatriz
authors: B
authors: Tavira
authors: Beatriz
authors: B
authors: Díaz-Molina
authors: Carlos
authors: C
authors: Morales
authors: César
authors: C
authors: Morís
authors: José L
authors: JL
authors: Rodríguez-Lambert
authors: Ana I
authors: AI
authors: Corao
authors: Marta
authors: M
authors: Díaz
authors: Victoria
authors: V
authors: Alvarez
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000483:Alleles; D024722:Cardiac Myosins / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000235:genetics*; D005091:Exons; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D020413:3' Untranslated Regions; C501641:MYH7 protein, human; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains