Prenatal diagnosis and genetic analysis of a family with hypertrophic cardiomyopathy
10.13602/j.cnki.jcls.2019.11.14
- VernacularTitle:1例肥厚型心肌病家系的产前诊断和遗传分析
- Author:
Xiaokang ZHANG
1
;
Jialing RONG
1
;
Siying HE
1
;
Guohua YANG
2
;
Bin LIANG
1
;
Yang XIANG
1
;
Jing LUO
1
;
Menglan LI
1
;
Jianhong MA
3
,
4
Author Information
1. Department of Clinical Laboratory, Zhongnan Hospital of Wuhan University
2. School of Basic Medicine Science, Wuhan University
3. Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University
4. Prenatal Diagnosis and Eugenics Clinical Medical Research Center of Hubei Province
- Publication Type:Journal Article
- Keywords:
hypertrophic cardiomyopathy;
prenatal diagnosis;
MYH7;
MYBPC3
- From:
Chinese Journal of Clinical Laboratory Science
2019;37(11):865-870
- CountryChina
- Language:Chinese
-
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.
