Mutations of ATP7B gene in two Thai siblings with Wilson disease
en Inglés
| IMSEAR
| ID: sea-129947
ABSTRACT
Background:
Wilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by mutations in ATP7B gene.Objective:
Report the clinical data and mutation analysis of two Thai siblings suspected of WD. Subject andmethods:
A 13-year-old boy who presented with cirrhosis, arthralgia, hypoalbuminemia, and coagulopathy, and his 11-year-old sister who was asymptomatic but had hepatomegaly with elevation of transaminases, were studied. Mutation analysis of ATP7B gene and mRNA analysis was performed in both patients and their parents.Results:
Investigations were consistent with WD, and their liver diseases improved after standard treatment for WD. DNA analyses in these two patients revealed two novel mutations, which were a deletion of the first 2bp of exon 6 (c.1870_1871delGA), and a single base substitution from A to G at nucleotide 4075 (c.4075A>G) in the exon 20 (p.M1359V). PCR-restriction digestion with NcoI restriction enzyme was employed as the second method for confirmation of the c.4075A>G mutation and for rapid screening in 100 chromosomes from unrelated healthy controls, and this variant was not present in the controls. The c.1870_1871delGA deletion caused a frameshift effect, which results in a premature stop codon (p.E624fsX753), and the p.M1359V mutation is a substitution of methionine with valine, which may have effects upon its orientation and interaction with other adjacent amino acids.Conclusion:
Two novel mutations of ATP7B gene were identified in two Thai siblings with WD.
Texto completo:
Disponible
Índice:
IMSEAR (Asia Sudoriental)
Idioma:
Inglés
Año:
2010
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