[Haplotype analysis and possible founder effect at the R778L mutation of the ATP7B gene in Korean patients with Wilson's disease].
Korean J Hepatol
; 15(3): 309-19, 2009 Sep.
Article
em Ko
| MEDLINE
| ID: mdl-19783880
ABSTRACT
BACKGROUND/AIMS:
Wilson's disease (WD) is an inherited disorder of copper metabolism caused by alteration of the P-type adenosine triphosphatase (ATP) 7B gene. In this study, we analyzed the frequency of well-known mutations and constructed the first haplotypes for Koreans. In addition, we evaluated whether a founder effect existed in Korean patients with WD.METHODS:
We obtained DNA samples from 21 patients with WD and their parents (total cohort n=63). ATP7B gene mutations were identified by direct sequencing methods, and microsatellite typing was performed at D13S315, D13S1325, and D13S316 with fluorescent dye-labeled primers. Any founder effect was identified by using 42 normal alleles from parents with a normal phenotype as a control group. The chi square test and Fisher's exact test were used for statistical analysis.RESULTS:
Three common mutations were found in 23 chromosomes obtained from 21 patients the R778L mutation at exon 8 (15/23, 65.2%), the A874V mutation at exon 11 (6/23, 26.1%), and the N1270S mutation at exon 18 (2/23, 8.7%). D13S315 and D13S316 showed linkage disequilibrium at alleles 5 and 4, respectively, in patients with the R778L mutation (P=0.0157 and 0.0001, respectively). The haplotype made up of these two alleles occurred significantly more frequently in patients with the R778L mutation (5-R778L-4, D13S315-mutation-D13S316) than in the controls (P=0.0018).CONCLUSIONS:
The arche haplotype of the ATP7B gene in Korean patients with WD may be 5-R778L-4 (D13S315.mutation.D13S316), and it might illustrate a founder effect.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Adenosina Trifosfatases
/
Efeito Fundador
/
Proteínas de Transporte de Cátions
/
Degeneração Hepatolenticular
/
Mutação
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
País como assunto:
Asia
Idioma:
Ko
Ano de publicação:
2009
Tipo de documento:
Article