Only one rare 3′ UTR variant (c.*29T>C) found in the patients was absent among the controls.
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. 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). Instead, we identified several new rare intronic variants. Lack of aberrant PCR fragments excluded single-exon deletions in the patients. We amplified and sequenced large MYH7 fragments in 60 HCM patients without previously identified sarcomere mutations. 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. MYH7 mutations are found in ∼20% of hypertrophic cardiomyopathy (HCM) patients.
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