title: Age-related penetrance of hereditary atypical hemolytic uremic syndrome.
abstract: 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.
authors: Department of Nephrology, Section of Preventive Medicine, University Medical Center, Albert-Ludwigs-University, Freiburg, Germany.
authors: Maren
authors: M
authors: Sullivan
authors: Lisa A
authors: LA
authors: Rybicki
authors: Aurelia
authors: A
authors: Winter
authors: Michael M
authors: MM
authors: Hoffmann
authors: Stefanie
authors: S
authors: Reiermann
authors: Hannah
authors: H
authors: Linke
authors: Klaus
authors: K
authors: Arbeiter
authors: Ludwig
authors: L
authors: Patzer
authors: Klemens
authors: K
authors: Budde
authors: Bernd
authors: B
authors: Hoppe
authors: Martin
authors: M
authors: Zeier
authors: Karl
authors: K
authors: Lhotta
authors: Andreas
authors: A
authors: Bock
authors: Thorsten
authors: T
authors: Wiech
authors: Ariana
authors: A
authors: Gaspert
authors: Thomas
authors: T
authors: Fehr
authors: Magdalena
authors: M
authors: Woznowski
authors: Gani
authors: G
authors: Berisha
authors: Angelica
authors: A
authors: Malinoc
authors: Oemer-Necmi
authors: ON
authors: Goek
authors: Charis
authors: C
authors: Eng
authors: Hartmut P H
authors: HP
authors: Neumann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D065766:Atypical Hemolytic Uremic Syndrome; D002648:Child; D017242:Complement Factor H / Q000235:genetics*; D017244:Complement Factor I; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics*; D006801:Humans; D008297:Male; D051916:Membrane Cofactor Protein / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D019683:Penetrance
chemical_list: D051916:Membrane Cofactor Protein; D017242:Complement Factor H; C493611:CFI protein, human; D017244:Complement Factor I