Direct Sequencing Analysis of Exon 14 of ATP7B Gene in Wilson Disease Patients
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- Category: Vol. 85, December 2017
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Direct Sequencing Analysis of Exon 14 of ATP7B Gene in Wilson Disease Patients, MONA FATHY, MARWA EL-SHARKAWY, RANIA ESSAM, HAZEM ABOU-YOUSSEF, NEHAD MOSAAD, HANAA ELKARAKSY, ENGY MOGAHED and MONA ABDULLATIF
Abstract
Background: Wilson Disease (WD) is caused by defects in copper-transporting P-type adenosine tri-phosphatase (AT-Pase) encoded by the ATP7B gene. Deposition of copper in liver and brain results in significant disability and death if left untreated. In certain populations, a high prevalence of particular mutations allows rapid screening and diagnosis of the disease.
Aim of Work: To study the WD related variants of ATP7B gene, exon 14 by direct sequencing in order to recommend an approach for diagnosis of Wilson disease tailored to the Egyptian community.
Subjects and Methods: The study included 39 WD children whose mean ages were 9.8±3.6 years. Genomic DNA was extracted from EDTA blood samples on which direct sequenc-ing for exon 14 of ATP7B gene was performed. Demographic, clinical, laboratory and histopathological data at the time of diagnosis were obtained.
Results: Four different substitutions were found among 10 cases (26%): c.3231C>T, c.3227A>G, c.3207C>A, and c.3138G>A, two are missense variation NP_000044.2 (p.T1076I, p.H1069Q) and two are silent variants (p.K1077K, p.G1046G) of which a silent novel variation c.3138G>A (p.G1046G) was found among two patients, in heterozygotes state.
Conclusion: Since it is possible to avoid the adverse effects of copper accumulation with early medical treatment, mutation analysis is an important diagnostic approach to confirm the disease with mild clinical symptoms. Analysis of the entire ATP7B gene instead of screening for hot mutations is useful due to its wide complex mutational spectrum.