A De Novo Deletion in the Regulators of Complement Activation Cluster Producing a Hybrid Complement Factor H/Complement Factor H-Related 3 Gene in Atypical Hemolytic Uremic Syndrome.
J Am Soc Nephrol
; 27(6): 1617-24, 2016 06.
Article
in En
| MEDLINE
| ID: mdl-26490391
ABSTRACT
The regulators of complement activation cluster at chromosome 1q32 contains the complement factor H (CFH) and five complement factor H-related (CFHR) genes. This area of the genome arose from several large genomic duplications, and these low-copy repeats can cause genome instability in this region. Genomic disorders affecting these genes have been described in atypical hemolytic uremic syndrome, arising commonly through nonallelic homologous recombination. We describe a novel CFH/CFHR3 hybrid gene secondary to a de novo 6.3-kb deletion that arose through microhomology-mediated end joining rather than nonallelic homologous recombination. We confirmed a transcript from this hybrid gene and showed a secreted protein product that lacks the recognition domain of factor H and exhibits impaired cell surface complement regulation. The fact that the formation of this hybrid gene arose as a de novo event suggests that this cluster is a dynamic area of the genome in which additional genomic disorders may arise.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Blood Proteins
/
Gene Deletion
/
Complement Activation
/
Atypical Hemolytic Uremic Syndrome
Limits:
Animals
/
Humans
Language:
En
Journal:
J Am Soc Nephrol
Journal subject:
NEFROLOGIA
Year:
2016
Document type:
Article