Age-Related Penetrance of Hereditary Atypical Hemolytic Uremic Syndrome

作者：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 Oemer Necmi; Eng Charis; Neumann Hartmut P H^*

来源：Annals of Human Genetics, 2011, 75: 639-647.

DOI：10.1111/j.1469-1809.2011.00671.x

• Hemolytic uremic syndrome
• complement factor H (CFH)
• complement factor I (CFI)
• membrane cofactor protein (MPC)
• CD46
• age-related penetrance estimations

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.

• 出版日期2011-11