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Age‐Related Penetrance of Hereditary Atypical Hemolytic Uremic Syndrome
Author(s) -
Sullivan Maren,
Rybicki Lisa A.,
Winter Aurelia,
Hoffmann Michael M,
Reiermann Stefanie,
Linke Hannah,
Arbeiter Klaus,
Patzer Ludwig,
Budde Klemens,
Hoppe Bernd,
Zeier Martin,
Lhotta Karl,
Bock Andreas,
Wiech Thorsten,
Gaspert Ariana,
Fehr Thomas,
Woznowski Magdalena,
Berisha Gani,
Malinoc Angelica,
Goek OemerNecmi,
Eng Charis,
Neumann Hartmut PH
Publication year - 2011
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1469-1809.2011.00671.x
Subject(s) - penetrance , atypical hemolytic uremic syndrome , medicine , germline mutation , mutation , genetics , index case , disease , gene mutation , gene , immunology , biology , phenotype , antibody , complement system
Summary 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.