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

• Published in: BMC medical genetics Vol. 19; no. 1; p. 104
• Main Authors: Huong, Nguyen Thi Mai, Lien, Nguyen Thi Kim, Ngoc, Ngo Diem, Mai, Nguyen Thi Phuong, Hoa, Nguyen Pham Anh, Hai, Le Thanh, Van Chi, Phan, Van, Ta Thanh, Van Khanh, Tran, Hoang, Nguyen Huy
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 18.06.2018; BioMed Central; BMC
• Subjects: Adenosine triphosphatase; ATP7B gene; Case Report; Cell death; Child; Children; Coding; Copper; Copper-transporting ATPases - genetics; Data processing; Deoxyribonucleic acid; DNA; Edema; Exons - genetics; Families & family life; Female; Gene mutation; Genetic analysis; Genetic aspects; Genetics; Genotype & phenotype; Health aspects; Hepatolenticular Degeneration - genetics; Hereditary diseases; Hospitalization; Humans; Liver; Liver diseases; Liver transplantation; Male; Medical diagnosis; Mutation; Mutation - genetics; Mutation of the ATP7B gene; Neurological complications; Oxidative stress; Paralysis; Patients; Proteins; Risk factors; Sleep disorders; Urine; Vietnamese (Southeast Asian people); Vietnamese patients; Vomiting; Wilson disease; Wilson's disease; United States > US; Vietnam; Wilson disease; Vietnamese patients; Mutation of the ATP7B gene
• ISSN: 1471-2350; 1471-2350
• DOI: 10.1186/s12881-018-0619-4

Wilson 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. We 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. In 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.