Analysis of genetic variants in a pedigree affected with hereditary multiple osteochondroma.
10.3760/cma.j.cn511374-20200415-00272
- Author:
Xiaoyan GUO
1
;
Qinqin ZHENG
;
Mingrui LIN
;
Yiyuan ZHANG
;
Tengfei SHI
Author Information
1. Department of Laboratory Medicine, Fuzhou Second Hospital Affiliated to Xiamen University, Fuzhou, Fujian 350007, China. shi_tf@163.com.
- Publication Type:Journal Article
- MeSH:
Codon, Nonsense;
Exons/genetics*;
Exostoses, Multiple Hereditary/genetics*;
Heterozygote;
Humans;
Pedigree
- From:
Chinese Journal of Medical Genetics
2021;38(6):549-552
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the genetic basis for a pedigree affected with hereditary multiple osteochondroma (HMO).
METHODS:Peripheral blood samples were collected from the proband and members of his pedigree with informed consent. Following extraction of genomic DNA, all coding exons and flanking intronic sequences (-10 bp) of the EXT1 and EXT2 genes were subjected to targeted capture and next generation sequencing (NGS). Suspected variant was verified by Sanger sequencing.
RESULTS:A heterozygous nonsense variant (c.1911C>A) was found in exon 10 of the EXT1 gene in the proband and his affected father but not in a healthy sister and normal controls. The variant was classified as a pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (PVS1+PM2+PP1). Bioinformatic analysis predicted that the c.1911C>A variant may be disease-causing via nonsense-mediated mRNA decay and anomalous splicing.
CONCLUSION:The c.1911C>A variant probably underlay the disease in this pedigree. Discovery of this variant enriched the variant spectrum of HMO.
