Prenatal diagnosis and genetic analysis of a family with hypertrophic cardiomyopathy / 临床检验杂志

ABSTRACT

Objective@#To explore the relationship between HCM pathogenic gene mutations and clinical phenotypes by analyzing the prenatal diagnosis and genetic characteristics of a pregnant woman from a family with hypertrophic cardiomyopathy (HCM). @*Methods@#The clinical data of the proband and her family members was collected. The DNA was extracted from the peripheral blood, amniotic fluid cells and cultured amniotic fluid cells of proband. Next generation sequencing (NGS) was utilized for screening pathogenetic loci of the proband. The suspected mutation sequences of HCM pathogenic candidate genes MYH7 and MYBPC3 were directly sequenced after PCR. Pathogenicity prediction of amniotic fluid cells was performed by using genetic data and bioinformatics software, such as Mutation taster, PolyPhen-2 and ANTHEPROT. @*Results@#The sequencing results showed that heterozygous mutations of MYH7 c.1988G＞A (p.Arg663His) and MYBPC3 c.151G＞A (p.Ala51Thr) were found in the proband. The phenotype of her father was normal, and no abnormal mutations were detectable. Her mother also showed normal phenotype but carried MYBPC3 c.151G＞A heterozygous mutation. Only MYH7 c.1988G＞A heterozygous mutation was found in the fetus and no abnormal variation of MYBPC3 was showed. The prediction of mutation effect and analysis of protein structure and function revealed that the two missense mutations could affect the hydrophobicity and antigenicity of the protein. The genetic data demonstrated MYH7 c.1988G＞A was defined as a pathogenic mutation. @*Conclusion@#MYH7 c.1988G＞A should be a newly generated pathogenic mutation in the proband, or caused by reproductive chimerism of her parents. MYBPC3 c.151G＞A mutation may promote the occurrence of HCM. Although the fetus only carries MYH7 c.1988G＞A, her phenotype may still display as HCM.