Clinical and genetic analysis of a Chinese pedigree affected with Dyggve-Melchior-Clausen syndrome due to a novel frameshift variant of DYM gene.
10.3760/cma.j.cn511374-20210127-00084
- VernacularTitle:一例
DYM基因移码变异所致Dyggve-Melchior-Clausen综合征患儿的临床及遗传学分析
- Author:
Lele KUANG
1
;
Rui PENG
;
Bin LIU
;
Di XI
;
Qiurong CHANG
;
Yuping GAO
Author Information
1. Department of Assisted Reproduction, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China. gaoyuping@xinhuamed.com.cn.
- Publication Type:Journal Article
- MeSH:
China;
Dwarfism/genetics*;
Humans;
Intellectual Disability;
Osteochondrodysplasias/genetics*;
Pedigree
- From:
Chinese Journal of Medical Genetics
2022;39(4):370-373
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the genetic basis of a Chinese pedigree affected with Dyggve-Melchior-Clausen syndrome.
METHODS:Whole exome sequencing and Sanger sequencing were carried out to detect potential pathogenic variants associated with the syndrome. The function of candidate variant was verified by Western blotting.
RESULTS:A novel homozygous variant, c.1222delG of the DYM gene was detected in the two affected siblings, for which both parents were heterozygous carriers. The variant has caused replacement of Asp by Met at amino acid 408 and generate a premature stop codon p.Asp408Metfs*10. Western blotting confirmed that the variant can result in degradation of the mutant DYM protein, suggesting that it is a loss of function variant.
CONCLUSION:The homozygous c.1222delG frameshift variant of the DYM probably underlay the Dyggve-Melchior-Clausen syndrome in the two affected siblings. Above findings has enabled clinical diagnosis and genetic counseling for the family.
