Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome.
Hum Mutat
; 31(6): E1445-60, 2010 Jun.
Article
in En
| MEDLINE
| ID: mdl-20513133
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Complement System Proteins
/
Complement Pathway, Alternative
/
Hemolytic-Uremic Syndrome
/
Mutation
Type of study:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Country/Region as subject:
America do norte
Language:
En
Journal:
Hum Mutat
Journal subject:
GENETICA MEDICA
Year:
2010
Document type:
Article
Affiliation country:
Estados Unidos