Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-50423
Sullivan, M; Rybicki, L A; Winter, A; Hoffmann, M M; Reiermann, S; Linke, H; Arbeiter, K; Patzer, L; Budde, K; Hoppe, B; Zeier, M; Lhotta, K; Bock, A; Wiech, T; Gaspert, A; Fehr, T; Woznowski, M; Berisha, G; Malinoc, A; Goek, O N; Eng, C; Neumann, H P H (2011). Age-related penetrance of hereditary atypical hemolytic uremic syndrome. Annals of Human Genetics, 75(6):639-647.
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Hereditary atypical hemolytic uremic syndrome (aHUS), a dramatic disease frequently leading to dialysis, is associated with germline mutations of the CFH, CD46, or CFI genes. After identification of the mutation in an affected aHUS patient, single-site gene testing of relatives is the preventive care perspective. However, clinical data for family counselling are scarce. From the German-Speaking-Countries-aHUS-Registry, 33 index patients with mutations were approached for permission to offer relatives screening for their family-specific mutations and to obtain demographic and clinical data. Mutation screening was performed using direct sequencing. Age-adjusted penetrance of aHUS was calculated for each gene in index cases and in mutation-positive relatives. Sixty-one relatives comprising 41 parents and 20 other relatives were enrolled and mutations detected in 31/61. In total, 40 research participants had germline mutations in CFH, 19 in CD46 and in 6 CFI. Penetrance at age 40 was markedly reduced in mutation-positive relatives compared to index patients overall with 10% versus 67% (P < 0.001); 6% vs. 67% (P < 0.001) in CFH mutation carriers and 21% vs. 70% (P= 0.003) in CD46 mutation carriers. Age-adjusted penetrance for hereditary aHUS is important to understand the disease, and if replicated in the future, for genetic counselling.
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology|
|Dewey Decimal Classification:||610 Medicine & health|
|Deposited On:||31 Oct 2011 09:43|
|Last Modified:||22 Dec 2013 16:09|
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