Document Detail

Two novel mutations of the GTP cyclohydrolase 1 gene and genotype-phenotype correlation in Chinese Dopa-responsive dystonia patients.
MedLine Citation:
PMID:  23211702     Owner:  NLM     Status:  MEDLINE    
The most common form of Dopa-responsive dystonia (DRD) is caused by heterozygous mutations in the GTP cyclohydrolase I (GCH1) gene. We screened two unrelated, DRD-symptomatic Chinese Han individuals, for GCH1 gene mutations by direct sequencing. As the clinical manifestations of DRD are highly variable, we also explored the association between genotype and phenotype in all Chinese DRD patients reported so far in the literature, comprising 62 DRD-affected patients from 36 Chinese families. Two novel missense mutations (T94M, L145F) and a novel variant (c. 453+6 G>T) were identified in our two new patients. None of these variants was detected in 200 healthy controls. On the basis of this and other reports, heterozygous mutations were detected in 90.3% of Chinese Han subjects with DRD. Seeming the age of onset for males and females, the mean age was 13 years older in males than in females (P=0.006). Different mutation types did not show any significant differences in age of onset, gender composition, initial symptoms, or the L-dopa dose that abolished the symptoms. Among DRD patients lacking missense or exon-intron boundary mutations, 68.4% were found to possess a large deletion in GCH1, which were detected by multiplex ligation-dependent probe amplification. Most GCH1 mutations were found to cluster in two regions of the coding sequence, suggesting the probable existence of mutation hotspot for the first time. The genotype-phenotype correlation described here may improve our understanding of DRD in Chinese individuals.
Lihua Yu; Huayong Zhou; Fayun Hu; Yanming Xu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-12-05
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  21     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-13     Completed Date:  2013-11-04     Revised Date:  2014-07-01    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  731-5     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Child, Preschool
Dystonic Disorders / complications,  diagnosis*,  genetics*,  pathology
GTP Cyclohydrolase / genetics*
Genetic Association Studies
Middle Aged
Mutation, Missense
Parkinsonian Disorders / complications,  genetics*,  pathology
Reg. No./Substance:
EC Cyclohydrolase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Genetic ancestry inference using support vector machines, and the active emergence of a unique Ameri...
Next Document:  Craniofacial characteristics of fragile X syndrome in mouse and man.