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Duplication in CFHR5: a New Culprit in Inherited Renal Disease an Internal Duplication Within the Gene from the Same Country

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Duplication in CFHR5: a New Culprit in Inherited Renal Disease an Internal Duplication Within the Gene from the Same Country RESEARCH HIGHLIGHTS GENETICS Duplication in CFHR5: a new culprit in inherited renal disease An internal duplication within the gene from the same country. We reasoned that that encodes complement factor-H-related they were likely to have the same genetic protein 5 (CFHR5) is responsible for problem, and this turned out to be the causing renal disease in individuals of case”, states Maxwell. Cypriot origin, say researchers. “We think The researchers then used a candidate this is the first clear example of such a gene approach to identify a novel variant change causing a highly penetrant disease”, that resulted in duplication of exons 2 and explains one of the study’s coauthors, 3 of CFHR5 in affected individuals. A PCR- Patrick Maxwell. based diagnostic test, developed by the findings provide evidence of an inherited To identify new genetic causes of renal researchers, was used to demonstrate renal disease, which they term CFHR5 disease, Maxwell and colleagues initially the presence of the mutation in additional nephropathy, charcterized by hematuria, performed genome-wide linkage analysis individuals from Cyprus or of Cypriot that may account for a substantial in two families from a London renal origin with unexplained hematuria or proportion of renal disease affecting transplant center. The families were both with end-stage renal disease of unknown Cypriots and their descendants worldwide. of Cypriot origin and had family members cause. By contrast, the researchers were Susan J. Allison who were affected by unusual renal unable to detect the CFHR5 duplication in disease that seemed to show an autosomal any of 36 individuals tested from the UK or Original article Gale, D. P. et al. Identification of a mutation dominant mode of inheritance. The France who had biopsy samples showing in complement factor H-related protein 5 in patients researchers identified a haplotype within C3 glomerulonephritis. of Cypriot origin with glomerulonephritis. Lancet 376, chromosome 1q31–32 that cosegregated Maxwell and colleagues say that their 794–801 (2010) with the occurrence of disease. “We findings imply that CFHR5 may be crucial Further reading Karumanchi, S. A. & Thadhani, R. had two pedigrees with a very rare, very in protecting the normal kidney from A complement to kidney disease: CFHR5 nephropathy. similar condition, who were originally immunological attack. They say that their Lancet 376, 748–750 (2010) NATURE REVIEWS | NEPHROLOGY VOLUME 6 | NOVEMBER 2010 | 632 © 2010 Macmillan Publishers Limited. All rights reserved.
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