Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome

Tara K Maga; Carla J Nishimura; Amy E Weaver; Kathy L Frees; Richard J H Smith

doi:10.1002/humu.21256

Back

Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome

Journal article

Peer reviewed

Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome

Tara K Maga, Carla J Nishimura, Amy E Weaver, Kathy L Frees and Richard J H Smith

Human mutation, Vol.31(6), pp.E1445-E1460

06/2010

DOI: 10.1002/humu.21256

PMID: 20513133

View Online

Abstract

Atypical hemolytic uremic syndrome (aHUS) is characterized by acute renal failure, thrombocytopenia and microangiopathic hemolytic anemia, and occurs with an estimated incidence in the USA of 2 per 1,000,000. Disease pathogenesis is related to dysregulation of the alternative pathway (AP) of the complement cascade at the level of the cell membrane secondary to mutations in a number of complement genes including complement factor H (CFH), complement factor H-related 5 (CFHR5), complement factor I (CFI), CD46 (MCP), complement factor B (CFB), complement component 3 (C3) and thrombomodulin (THBD). Since aHUS is rare, mutation rate data in large patient cohorts are scarce. Here we present the first cohort of American patients in whom mutation screening was completed on all genes currently implicated in aHUS. In addition to identifying a number of novel variants, we provide information on the relative frequency of mutations in these genes in an American aHUS population. Twelve percent (12%) of patients carrying disease-associated genetic variants segregated mutations in more than one gene mandating comprehensive genetic testing in the diagnosis and management of these patients.

United States - epidemiology

Genetic Predisposition to Disease

Gene Frequency

Humans

Complement Factor I - genetics

Hemolytic-Uremic Syndrome - epidemiology

Incidence

Hemolytic-Uremic Syndrome - genetics

Complement Factor B - genetics

DNA Mutational Analysis

Complement System Proteins - genetics

Membrane Cofactor Protein - genetics

Complement Pathway, Alternative - genetics

Mutation

Thrombomodulin - genetics

Complement Factor H - genetics

Complement C3 - genetics

Cohort Studies

Details

Title: Subtitle: Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome
Creators: Tara K Maga - Interdepartmental PhD Program in Genetics, Division of Nephrology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Carla J Nishimura
Amy E Weaver
Kathy L Frees
Richard J H Smith
Resource Type: Journal article
Publication Details: Human mutation, Vol.31(6), pp.E1445-E1460
DOI: 10.1002/humu.21256
PMID: 20513133
NLM abbreviation: Hum Mutat
ISSN: 1098-1004
eISSN: 1098-1004
Publisher: United States
Language: English
Date published: 06/2010
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Otolaryngology; Internal Medicine
Record Identifier: 9984006441402771

Metrics

29 Record Views

252 Times Cited - Web of Science

See more details