Three novel mutations in the ATP7B gene of unrelated Vietnamese patients with Wilson disease

Abstract

BackgroundWilson disease (OMIM # 277900) is a autosomal recessive disorder characterized by accumulation of copper in liver and brain. The accumulation of copper resulting in oxidative stress and eventually cell death. The disease has an onset in a childhood and result in a significant neurological impairment or require lifelong treatment. Another serious consequence of the disease is the development of liver damage and acute liver failure leading to liver transplant. The disorder is caused by mutations in the ATP7B gene, encoding a P-type copper transporting ATPase.Case presentationWe performed genetic analysis of three unrelated patients from three different Vietnamese families. These patients had clinical features such as numbness of hands and feet, vomiting, insomnia, palsy, liver failure and Kayser–Fleischer (K–F) rings and were diagnosed with Wilson disease in the Human Genetics Department, Vietnam National Children’s Hospital. The entire coding region and adjacent splice sites of ATP7B gene were amplified and sequenced by Sanger method. Sequencing data were analyzed and compared with the ATP7B gene sequence published in Ensembl (ENSG00000123191) by using BioEdit software to detect mutations.ConclusionsIn this study, five mutations in the ATP7B gene were found. Among of these, three mutations were novel: c.750_751insG (p.His251Alafs*19) in exon 2, c.2604delC (p.Pro868Profs*5) in exon 11, and c.3077 T > A (p.Phe1026Tyr) in exon 14. Our results of the mutations associated with Wilson disease might facilitate the development of effective treatment plans.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0619-4) contains supplementary material, which is available to authorized users.

Functional characterization of novel or yet uncharacterized ATP7B missense variants detected in patients with clinical Wilson's disease

“…The variant F1304 can form π-π interactions with the residue F1026, potentially displacing the catalytic D1027 from a perfect placement for transient phosphorylation. The importance of residue F1026 is further corroborated through a known WD-causing variant, F1026Y 46 .…”

Biliary atresia combined Wilson disease identified by whole exome sequencing in Vietnamese patient with severe liver failure

“…The mutations in the ATP7B gene have been evaluated as pathogenic mutations in the ClinVar database and previous studies. [ 6 ] The patient also carried a homozygous variant (p.Val444Ala) in the ABCB11 gene (Fig. 2 ).…”

“…To validate mutations, the exons and exon-intron boundaries of related genes were amplified and analyzed by direct sequencing. PCR reactions were performed according to previous publications to amplify the exons carrying the mutations in the ATP7B and ABCB11 genes [5,6] . For mutation in the KRT18 gene, we used primer pairs of forward primer 5′-CAGCATGAGCTTCACCACTC-3′ and reverse primer 5′-GGGAGTTGAGGTTCCCTCCTA-3′ to amplify and sequence.…”

Wilson's Disease Manifestation in Late Adulthood: A Case Report and Literature Review

“…Copper tends to build up in the liver, brain, kidneys, and cornea in WD, leading to a variety of symptoms including hepatic illness, neuronal degeneration in the brain, and Kayser-Fleischer (KF) rings at the corneal limbus [ 2 ]. An indication of WD includes low copper levels in the blood and ceruloplasmin, increased excretion of copper in the urine, and increasing hepatic copper levels [ 3 ]. Contrarily, successful molecular testing is still diagnostic [ 1 ].…”