Detection and analysis of an ATP2A2 mutation in a family with Darier-White disease.
10.3760/cma.j.issn.1003-9406.2019.08.010
- Author:
Xihui CHEN
1
;
Qingbo LIU
;
Mao SUN
;
Lijuan YUAN
;
Yuanming WU
Author Information
1. Department of Biochemistry and Molecular Biology, Center for DNA Typing, the Fourth Military Medical University, Xi' an, Shaanxi 710032, China. wuym@fmmu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Darier Disease;
genetics;
Heterozygote;
Humans;
Mutation, Missense;
Pedigree;
Sarcoplasmic Reticulum Calcium-Transporting ATPases;
genetics
- From:
Chinese Journal of Medical Genetics
2019;36(8):794-797
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the molecular basis for a pedigree affected with Darier-White disease.
METHODS:Genomic DNA was isolated from 3 patients and 1 unaffected member from the pedigree, as well as 80 healthy controls. Targeted sequence capture and next-generation sequencing were used to screen mutations of skin disease-related genes. Candidate mutations were verified by Sanger sequencing, and co-segregation analysis was carried out to confirm the pathogenicity of mutation. Conservation analysis and protein structure and function were also predicted with Bioinformatic tools.
RESULTS:A heterozygous mutation c.2246G>T (p.G749V) was identified in exon 15 of ATP2A2 gene in all 3 patients from the pedigree, but not in the unaffected member or 80 healthy controls. The corresponding amino acid was highly conserved, and mutation of which can lead to structural and functional changes of the protein.
CONCLUSION:The c.2246G>T missense mutation of the ATP2A2 gene probably underlies the Darier-White disease in this pedigree by causing damages to the structure and function of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2).
