Atypical haemolytic uraemic syndrome associated with a hybrid complement gene.
PLoS Med
; 3(10): e431, 2006 Oct.
Article
em En
| MEDLINE
| ID: mdl-17076561
ABSTRACT
BACKGROUND:
Sequence analysis of the regulators of complement activation (RCA) cluster of genes at chromosome position 1q32 shows evidence of several large genomic duplications. These duplications have resulted in a high degree of sequence identity between the gene for factor H (CFH) and the genes for the five factor H-related proteins (CFHL1-5; aliases CFHR1-5). CFH mutations have been described in association with atypical haemolytic uraemic syndrome (aHUS). The majority of the mutations are missense changes that cluster in the C-terminal region and impair the ability of factor H to regulate surface-bound C3b. Some have arisen as a result of gene conversion between CFH and CFHL1. In this study we tested the hypothesis that nonallelic homologous recombination between low-copy repeats in the RCA cluster could result in the formation of a hybrid CFH/CFHL1 gene that predisposes to the development of aHUS. METHODS ANDFINDINGS:
In a family with many cases of aHUS that segregate with the RCA cluster we used cDNA analysis, gene sequencing, and Southern blotting to show that affected individuals carry a heterozygous CFH/CFHL1 hybrid gene in which exons 1-21 are derived from CFH and exons 22/23 from CFHL1. This hybrid encodes a protein product identical to a functionally significant CFH mutant (c.3572C>T, S1191L and c.3590T>C, V1197A) that has been previously described in association with aHUS.CONCLUSIONS:
CFH mutation screening is recommended in all aHUS patients prior to renal transplantation because of the high risk of disease recurrence post-transplant in those known to have a CFH mutation. Because of our finding it will be necessary to implement additional screening strategies that will detect a hybrid CFH/CFHL1 gene.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Mutantes Quiméricas
/
Síndrome Hemolítico-Urêmica
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
PLoS Med
Assunto da revista:
MEDICINA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Reino Unido