Genetics of Wilson disease and Wilson‐like phenotype in a clinical series from eastern Spain

• Published in: Clinical genetics Vol. 97; no. 5; pp. 758 - 763
• Main Authors: Sánchez‐Monteagudo, Ana, Álvarez‐Sauco, María, Sastre, Isabel, Martínez‐Torres, Irene, Lupo, Vincenzo, Berenguer, Marina, Espinós, Carmen
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2020
• Subjects: ATP7B gene; CCDC115 gene; Diagnosis; Exons; Genetic analysis; genetic diagnosis; Genetic screening; Glycosylation; Hereditary diseases; Introns; Mutation; Phenotypes; targeted next‐generation sequencing; whole exome sequencing; Wilson's disease; Wilson‐like phenotype; Spain; targeted next-generation sequencing; genetic diagnosis; CCDC115 gene; Wilson's disease; whole exome sequencing; ATP7B gene; Wilson-like phenotype
• ISSN: 0009-9163; 1399-0004; 1399-0004
• DOI: 10.1111/cge.13719

Wilson's disease (WD) is an autosomal recessive disorder caused by ATP7B mutations. Subjects with only one mutation may show clinical signs and individuals with biallelic changes may remain asymptomatic. We aimed to achieve a conclusive genetic diagnosis for 34 patients clinically diagnosed of WD. Genetic analysis comprised from analysis of exons to WES (whole exome sequencing), including promoter, introns, UTRs (untranslated regions), besides of study of large deletions/duplications by MLPA (multiplex ligation‐dependent probe amplification). Biallelic ATP7B mutations were identified in 30 patients, so that four patients were analyzed using WES. Two affected siblings resulted to be compound heterozygous for mutations in CCDC115, which is involved in a form of congenital disorder of glycosylation. In sum, the majority of patients with a WD phenotype carry ATP7B mutations. However, if genetic diagnosis is not achieved, additional genes should be considered because other disorders may mimic WD.