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

作者：Challis Rachel C; Araujo Geisilaine S R; Wong Edwin K S; Anderson Holly E; Awan Atif; Dorman Anthony M; Waldron Mary; Wilson Valerie; Brocklebank Vicky; Strain Lisa; Morgan B Paul; Harris Claire L; Marchbank Kevin J; Goodship Timothy H J; Kavanagh David

来源：Journal of the American Society of Nephrology, 2016, 27(6): 1617-1624.

DOI：10.1681/ASN.2015010100

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.

• 出版日期2016-6
• 单位河北医科大学