High prevalence of the H1069Q mutation in East German patients with Wilson disease: rapid detection of mutations by limited sequencing and phenotype-genotype analysis.
J Hepatol
; 35(5): 575-81, 2001 Nov.
Article
en En
| MEDLINE
| ID: mdl-11690702
ABSTRACT
BACKGROUND/AIMS:
Wilson disease is caused by a large number of different mutations in the ATP7B gene. Wilson disease patients from a homogeneous ethnical background (Saxonia) were studied for distribution and phenotypes of ATP7B mutations.METHODS:
Eighty-two patients were analyzed. The H1069Q mutation was assayed by a polymerase chain reaction-based restriction fragment length polymorphism test. Exons 8 and 15 were sequenced in all, and the entire gene in 30, non-H1069Q-homozygotes.RESULTS:
Four novel and 12 known mutations were found. Thirty-two (39%) Wilson disease patients were homozygous and 39 (48%) heterozygous for the H1069Q mutation (allele frequency 63%). Together with sequence analysis of exons 8 and 15 mutations in both alleles were identified in 65% of patients. Only one patient had both mutations at other locations. In H1069Q homozygotes symptoms started later (21.3+/-7.2 years) than in H1069Q compound heterozygotes (14.6+/-5.8, P<0.001) or H1069Q negatives (10+/-4.4, P<0.001), and they had more frequently neurologic symptoms (93 vs. 47%, P<0.001) and Kayser-Fleischer rings (82 vs. 51%, P<0.001). Mutation status did not correlate with liver biopsy findings, serum ceruloplasmin levels or (64)Cu-assay results.CONCLUSIONS:
In spite of many known ATP7B mutations, only few occur in this homogeneous population. Limited genetic testing is useful to confirm Wilson disease in this population.
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Colección:
01-internacional
Asunto principal:
Polimorfismo de Longitud del Fragmento de Restricción
/
Adenosina Trifosfatasas
/
Proteínas de Transporte de Catión
/
Degeneración Hepatolenticular
/
Mutación
Tipo de estudio:
Diagnostic_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
País/Región como asunto:
Europa
Idioma:
En
Revista:
J Hepatol
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2001
Tipo del documento:
Article
País de afiliación:
Alemania