Analysis of genetic variants in five pedigrees affected with Dysferlinopathy.
10.3760/cma.j.cn511374-20200228-00112
- Author:
Yanjie XIA
1
;
Panlai SHI
;
Yaqin HOU
;
Duo CHEN
;
Peng DAI
;
Xinyu ZHAO
;
Xiangdong KONG
Author Information
1. Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. kongxd@263.net.
- Publication Type:Journal Article
- MeSH:
Humans;
Muscular Dystrophies, Limb-Girdle/genetics*;
Mutation;
Pedigree;
Phenotype;
RNA Splicing
- From:
Chinese Journal of Medical Genetics
2021;38(3):205-209
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To analyze the clinical phenotype and genetic variants in five Chinese pedigrees affected with Dysferlinopathy.
METHODS:Next generation sequencing (NGS) was carried out for the probands from the five pedigrees. Suspected variants were validated by Sanger sequencing. Pathogenicity of the variants was assessed based on the standards and guidelines by the American College of Medical Genetics and Genomics (ACMG).
RESULTS:Ten DYSF gene variants (including 5 frameshift variants, 3 splicing variants, 1 missense variant and 1 nonsense variant) were detected. Among these, c.1375dupA (p.Met459Asnfs*15), c.610C>T (p.Arg204X), c.1180+5G>A and c.1284+2T>C were known to be pathogenic, while c.4008_4010delCCTinsAC (p.Leu1337Argfs*8), c.1137_1169del (p.379_390del), c.754A>G(p.Thr252Ala), c.1175_1176insGCAGAGTG (p.Met394Serfs*7), c.3114_3115insCGGC (p.Arg1040Profs*74) and c.1053+3G>C were unreported previously. Of the six novel variants, c.1137_1169del, c.1175_1176insGCAGAGTG and c.3114_3115insCGGC were predicted as pathogenic (PVS1+PM2+PM3), c.4008_4010delCCTinsAC as likely pathogenic (PVS1+PM2), c.754A>G and c.1053+3G>C as variants of uncertain significance based on the ACMG standards and guidelines.
CONCLUSION:Variants of the DYSF gene probably underlay Dysferlinopathy in the patients among the five pedigrees. Above finding has enriched the spectrum of DYSF gene variants.
