title: A new mutational mechanism for hypertrophic cardiomyopathy.
abstract: We describe a male patient affected by hypertrophic cardiomyopathy (HCM) with no point mutations in the eight sarcomeric genes most commonly involved in the disease. By multiple ligation-dependent probe amplification (MLPA) we have identified a multi-exons C-terminus deletion in the cardiac myosin binding protein C (MYBPC3) gene. The rearrangement has been confirmed by long PCR and breakpoints have been defined by sequencing. The 3.5 kb terminal deletion is mediated by Alu-repeat elements and is predicted to result in haploinsufficiency of MYBPC3. To exclude the presence of other rare pathogenic variants in additional HCM genes, we performed targeted next-generation sequencing (NGS) of 88 cardiomyopathy-associated genes but we did not identify any further mutation. Interestingly, the MYBPC3 multi-exons deletion was detectable by NGS. This finding broadens the range of mutational spectrum observed in HCM, contributing to understanding the genetic basis of the most common inherited cardiovascular disease. Moreover, our data suggest that NGS may represent a new tool to achieve a deeper insight into molecular basis of complex diseases, allowing to detect in a single experiment both point mutations and gene rearrangements.
authors: USSD Laboratorio Genetica Medica, Ospedali Riuniti, Bergamo, Italy.
authors: Laura
authors: L
authors: Pezzoli
authors: Maria Elena
authors: ME
authors: Sana
authors: Paolo
authors: P
authors: Ferrazzi
authors: Maria
authors: M
authors: Iascone
mesh_terms: D000293:Adolescent; D020087:Alu Elements; D001483:Base Sequence; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005091:Exons; D005260:Female; D015321:Gene Rearrangement; D057895:Haploinsufficiency; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017384:Sequence Deletion; D020107:Troponin T / Q000235:genetics; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D004247:DNA; D020107:Troponin T; D000099163:Myosin Binding Protein C; C545568:TNNT2 protein, human