Mutation screening and prenatal diagnosis of Wilson's disease by denature high performance liquid chromatography / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To study the clinical application of denature high performance liquid chromatography (DHPLC) technique on mutation screening and prenatal diagnosis for Wilson's disease (WD).</p><p><b>METHODS</b>Genomic DNA of the probands with Wilson's disease and their parents from 6 families was subjected to polymerase chain reaction (PCR) for the 21 exons and the 5' untranslated region of ATP7B gene. Mutation screening of the PCR products was performed by DHPLC. The abnormal peaks were confirmed by further sequencing analysis. Based on the successful gene diagnosis for the patients, prenatal diagnosis was performed in 4 families, including 1 twin and 3 singletons.</p><p><b>RESULTS</b>Five disease-causing mutations and 8 polymorphisms were found in the 6 probands by DHPLC and sequencing. The parents were carriers with the same mutation as their affected children. Prenatal diagnosis showed that two pregnancies were abnormal, including a twin pregnancy with compound heterozygote for Arg778Leu and IVS4-1G>C mutation, and a single pregnancy with a compound heterozygote for Ser975Tyr and Pro992Leu mutations. These two pregnancies were terminated after genetic counseling. Another two pregnancies included a singleton carrier with Ser975Tyr mutation and a normal genotype fetus, respectively. These two pregnancies were continued and the babies were healthy.</p><p><b>CONCLUSION</b>DHPLC is a powerful tool in prenatal diagnosis as well as in postnatal diagnosis.</p>