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

Autores de CIPF

• Ana Sánchez Monteagudo

  Autor

• Vincenzo Lupo

  Autor

• 

  Carmen Espinós Armero

  Autor

Participantes ajenos a CIPF

• Alvarez-Sauco, M
• Sastre, I
• Martinez-Torres, I
• Berenguer, M

Grupos de Investigación

• Laboratorio de Enfermedades Raras Neurodegenerativas

Abstract

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.

Keywords

• ATP7B gene; CCDC115 gene; genetic diagnosis; targeted next-generation sequencing; whole exome sequencing; Wilson's disease; Wilson-like phenotype