Study of gene mutation and pathogenetic mechanism for a family with Waardenburg syndrome.
- VernacularTitle:一个Waardenburg综合征家系的基因突变及致病机制分析
- Author:
Hongsheng CHEN
1
;
Xinbin LIAO
;
Yalan LIU
;
Chufeng HE
;
Hua ZHANG
;
Lu JIANG
;
Yong FENG
;
Lingyun MEI
Author Information
- Publication Type:Journal Article
- MeSH: Adolescent; Adult; Case-Control Studies; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Mutation; genetics; Pedigree; Waardenburg Syndrome; genetics; Young Adult
- From: Chinese Journal of Medical Genetics 2017;34(4):471-475
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the pathogenetic mechanism of a family affected with Waardenburg syndrome.
METHODSClinical data of the family was collected. Potential mutation of the MITF, SOX10 and SNAI2 genes were screened. Plasmids for wild type (WT) and mutant MITF proteins were constructed to determine their exogenous expression and subcellular distribution by Western blotting and immunofluorescence assay, respectively.
RESULTSA heterozygous c.763C>T (p.R255X) mutation was detected in exon 8 of the MITF gene in the proband and all other patients from the family. No pathological mutation of the SOX10 and SNAI2 genes was detected. The DNA sequences of plasmids of MITFand mutant MITFwere confirmed. Both proteins were detected with the expected size. WT MITF protein only localized in the nucleus, whereas R255X protein showed aberrant localization in the nucleus as well as the cytoplasm.
CONCLUSIONThe c.763C>T mutation of the MITF gene probably underlies the disease in this family. The mutation can affect the subcellular distribution of MITF proteins in vitro, which may shed light on the molecular mechanism of Waardenburg syndrome caused by mutations of the MITF gene.
