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Common local founder effects for Wilson's disease and hereditary hemochromatosis: mutation studies of a large family
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Science for Life Laboratory, SciLifeLab, Science for Life Laboratory, SciLifeLab. (Endokrinologi och mineralmetabolism, Endocrinology and mineral metabolism)ORCID iD: 0000-0002-2650-5926
2012 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 47, no 8-9, 1014-1020 p.Article in journal (Refereed) Published
Abstract [en]

Wilson's disease (WND) and hereditary hemochromatosis (HH) are two metal loading diseases of copper and iron, respectively, and are both recessively inherited. In central Sweden, where HH is common, 9 Wilson kindred (14 members) were identified. Aims of the study were to test whether nine WND families shared a common origin, a common mutation and if carrying HFE mutations affected their phenotype Results. The nine families were traced through 13 generations to a common founder origin in the mid-seventeenth century. Despite identity of descent, four different ATP7B mutations appeared with homozygosity in four, with two different mutations, W779X and T977M. There were three compound heterozygotes, W779X/T977M, R1319X/H1069Q and one T977M combined with a new, previously not described mutation, probably of Finnish origin. The founder family also included 26 descendant kindred (55 members) with HH as shown by HFE mutations. This admixture coincided with a migration out of the original parish into hemochromatosis-rich localities. One WND patient had iron overload (serum ferritin 672 mu g/l and raised liver enzymes), but lacked HFE mutations. In another family with serious hemochromatosis (two sons dying from bronze diabetes), the coinheritance of congenital spherocytosis was probably the cause rather than an additional effect of WND. Conclusions. WND though a rare disease may become aggregated like HH in certain areas due to local founder effects. Despite extensive pedigree studies leading back to the local founder family, the authors were unable to find a single defining mutation of the ATP7B gene.

Place, publisher, year, edition, pages
2012. Vol. 47, no 8-9, 1014-1020 p.
Keyword [en]
ATP7B mutations, congenital spherocytosis, hereditary hemochromatosis, iron, pedigrees, Wilson's disease
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-182017DOI: 10.3109/00365521.2012.703240ISI: 000308213200019OAI: oai:DiVA.org:uu-182017DiVA: diva2:559189
Available from: 2012-10-08 Created: 2012-10-02 Last updated: 2016-02-29

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