Molecular Analysis of Wilson Disease
Vrábelová S. , Váňová P., Kopečková L. , 1Trunečka P., 2Smolka V., Procházková D., 3Vejvalková Š., 4Šuláková A., 5Kupčová V., 6Bzdúch V., Kozák L.
Výzkumný ústav zdraví dítěte, oddělení biochemické a molekulární genetiky, Brno 1Institut klinické a experimentální medicíny, Praha 2Fakultní nemocnice. Olomouc 3Ústav biologie a lékařské genetiky FNM, Praha 4Klinika dětského lékařství FNsP, Ostrava-Poruba 5III. interní klinika LF UK, Bratislava 6I. dětská klinika DFNsP, Bratislava |
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Summary:
Background. Wilson disease is an autosomal recessive disorder, characterized by cooper accumulation and
intoxication of the organism. Molecular basis of the disease represent mutations in the gene for the copper-transporting
ATPase (ATP7B).
Methods and Results. The submitted paper deals with results of molecular-genetic examination in 130 unrelated
families in whichWilson disease was diagnosed. By denaturing gradient gel electrophoresis (DGGE), the exons with
abnormal sequences were detected. Followed by sequencing, 17 causal mutations and 9 silent polymorphism were
found. Five novel mutations were detected. After analysis of 260 mutant alleles, 214 (82.3 %) were identified. The
most frequent mutation, H1069Q, occurred in our population with the frequency of 65.8 %. Incidence of other
mutations, however, did not exceed 5 %.
Conclusions. DNA analysis of the Wilson disease offers prompt and reliable results in affected families. It can
help to identify asymptomatic and heterozygote siblings at genetic counselling.
Key words:
Wilson disease, ATP7B gene, mutation, DNA diagnosis.
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