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Autosomal recessive transmission of MYBPC3 mutation results in malignant phenotype of hypertrophic cardiomyopathy
Journal article   Open access   Peer reviewed

Autosomal recessive transmission of MYBPC3 mutation results in malignant phenotype of hypertrophic cardiomyopathy

Yilu Wang, Zhimin Wang, Qi Yang, Yubao Zou, Hongju Zhang, Chaowu Yan, Xinxing Feng, Yi Chen, Yin Zhang, Jizheng Wang, …
PloS one, Vol.8(6), pp.e67087-e67087
2013
DOI: 10.1371/journal.pone.0067087
PMCID: PMC3695947
PMID: 23840593
url
https://doi.org/10.1371/journal.pone.0067087View
Published (Version of record) Open Access

Abstract

Hypertrophic cardiomyopathy (HCM) due to mutations in genes encoding sarcomere proteins is most commonly inherited as an autosomal dominant trait. Since nearly 50% of HCM cases occur in the absence of a family history, a recessive inheritance pattern may be involved. A pedigree was identified with suspected autosomal recessive transmission of HCM. Twenty-six HCM-related genes were comprehensively screened for mutations in the proband with targeted second generation sequencing, and the identified mutation was confirmed with bi-directional Sanger sequencing in all family members and 376 healthy controls. A novel missense mutation (c.1469G>T, p.Gly490Val) in exon 17 of MYBPC3 was identified. Two siblings with HCM were homozygous for this mutation, whereas other family members were either heterozygous or wild type. Clinical evaluation showed that both homozygotes manifested a typical HCM presentation, but none of others, including 5 adult heterozygous mutation carriers up to 71 years of age, had any clinical evidence of HCM. Our data identified a MYBPC3 mutation in HCM, which appeared autosomal recessively inherited in this family. The absence of a family history of clinical HCM may be due to not only a de novo mutation, but also recessive mutations that failed to produce a clinical phenotype in heterozygous family members. Therefore, consideration of recessive mutations leading to HCM is essential for risk stratification and genetic counseling.
 Phenotype Ultrasonography Humans Middle Aged Child, Preschool Molecular Sequence Data Male Mutation, Missense Young Adult Base Sequence Adult Female Cardiomyopathy, Hypertrophic - diagnostic imaging Child Myocardial Contraction Amino Acid Sequence Cardiomyopathy, Hypertrophic - genetics Genetic Association Studies Myocardium - pathology Genes, Recessive Sequence Analysis, DNA Carrier Proteins - genetics Homozygote Cardiomyopathy, Hypertrophic - physiopathology Pedigree Heterozygote Aged High-Throughput Nucleotide Sequencing

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