Phenotypic heterogeneity and gene penetrance of a dopa-responsive dystonia family
10.3760/cma.j.cn115354-20220630-00461
- VernacularTitle:多巴反应性肌张力障碍一家系临床异质性和基因外显率研究
- Author:
Qing SUN
1
;
Renbin WANG
;
Kang WANG
;
Xiaohui DUAN
;
Li YAN
;
Dantao PENG
Author Information
1. 中日友好医院神经科，北京 100029
- Keywords:
Dopa-responsive dystonia;
GTP cyclohydrolase 1;
Gene penetrance
- From:
Chinese Journal of Neuromedicine
2022;21(11):1153-1157
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the phenotypic heterogeneity and gene penetrance of a dopa-responsive dystonia (DRD) family.Methods:The clinical data of a four-generation DRD family (including 3 patients) admitted to Department of Neurology, China-Japan Friendship Hospital in November 2015 were retrospectively analyzed. The proband underwent whole exon sequence, and the genetic result was verified by Sanger sequencing. Sanger sequencing was performed in the other 14 subjects in the family; the genotypes and clinical manifestations were analyzed.Results:In 15 subjects underwent genetic testing, 7 had heterozygous mutations c.284G>A (p.P95L) in GCH1 gene; the penetrance of GCH1 gene mutation in this family was 0.43 (3/7), the gene penetrance in male was 0.25 (1/4), and the gene penetrance in female was 0.67 (2/3). Three subjects in the DRD family had clinical symptoms; the clinical symptoms of the two female patients were more severe than those of the male patient; the severity of clinical symptoms differed greatly between the 2 female patients. Conclusion:There is a wide intrafamilial phenotypic heterogeneity in DRD family members carrying the same gene mutation, and the phenotype is gender-related; the gene penetrance in male is lower than that in female, and the clinical phenotype is often milder.
