Wilson disease in Iceland: a clinical and genetic study

• Main Authors: Thomas, G R, Jensson, O, Gudmundsson, G, Thorsteinsson, L, Cox, D W
• Other Authors: Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
• Format: Article in Journal/Newspaper
• Language: English
• Published: University of Chicago Press 2011
• Subjects: Adolescent; Adult; Alternative Splicing; Base Sequence; Ceruloplasmin; Copper; Female; Founder Effect; Haplotypes; Hepatolenticular Degeneration; Humans; Iceland; Male; Molecular Sequence Data; Pedigree; Polymerase Chain Reaction; Prevalence; Sequence Deletion
• Online Access: http://hdl.handle.net/2336/119270

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field A survey of Wilson disease in Iceland has revealed two large kindreds with affected individuals. We have carried out studies of haplotypes of dinucleotide repeat polymorphisms (CA repeats) flanking the Wilson disease gene. The same mutation, a 7-bp deletion, is present in both families, and the clinical features are similar. The haplotype data and nature of the mutation support the existence of a founder chromosome carrying the mutation. This Icelandic mutation was not found in patients of Irish or Scottish origins, who could share some of the Icelandic ancestral genes. Although the protein function is predicted to be completely abolished by the deletion, predicting early-onset liver disease, we find that the patients present with later-onset neurological and psychiatric symptoms. We show that alternative splicing of the transcript in the region of the deletion could contribute to later onset, suggesting that alternative isoforms of the protein might have some functional significance.