Atypical haemolytic uraemic syndromeGene: CFHR5
Comment on list classification: Changing rating from grey to amber. Some evidence to suggest that variants in CFHR5 may be associated with aHUS but there are not 3 clear cases with variants only found in that gene and segregation data, or functional data
Created: 21 Mar 2020, 2:58 p.m. | Last Modified: 21 Mar 2020, 2:58 p.m.
Panel Version: 2.5
Associated with Nephropathy due to CFHR5 deficiency #614809 (AD) in OMIM.
Some evidence to suggest that variants in CFHR5 may be associated with aHUS but there are not 3 clear cases with variants only found in that gene and segregation data, or functional data.
PMID: 20513133 - Maga et al 2010 - looked for variants in CFH, CFHR5, CFI, CD46, CFB, C3 and THBD in 144 American aHUS patients. 4 patients with 3 different variants in CFHR5 were identified (c.223G>T p.E75X, c.836T>A p.Y277N, c. 1135 G>C p.V379L). But 2 patients also had variants in other candidate genes.
PMID: 22622361- Westra et al 2012 - screened 65 aHUS patients for mutations in CFHR5. Found 3 patients that had different heterozygous variants `(9c.314T>G p.Leu105Arg, c.583T>A p.Ser195Thr, c.1308G>T p.Trp436Cys) that are rare (not found in 1000 Genomes Project, or Exome Variant Server), all prediction programs predict them to be damaging to protein function, and no other genetic variations were identified in these patients yet. No functional studies. No segregation data. OMIM list the 3 variants as VUS.
PMID: 29500241 - Osborne et al 2018 - looked at results of CFHR5 screening in 315 aHUS patients. Other genes were screened as well. Report that 3 rare variants found in CFHR5 but information about variants and cases not given.
PMID: 30905589 - Tseng et al 2019 - WES of 10 aHUS patients - 1 patient (patient 9) with variants found in CFH, CFHR5 (c. G700A, E234K)., and MASP1 genes presented with fulminant heart failure with acute kidney injury and died before initiation of plasma therapy.
Created: 29 Jan 2020, 4:24 p.m. | Last Modified: 29 Jan 2020, 4:24 p.m.
Panel Version: 2.1
There is at least one paper specifically linking variants in this gene with aHUS, not quite sure where this gene belongs.
Sources: Expert list
Created: 9 Jan 2020, 4:16 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Nephropathy due to CFHR5 deficiency, MIM# 614809
Gene: cfhr5 has been classified as Amber List (Moderate Evidence).
Publications for gene: CFHR5 were set to 22622361
gene: CFHR5 was added gene: CFHR5 was added to Atypical haemolytic uraemic syndrome. Sources: Expert list Mode of inheritance for gene: CFHR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CFHR5 were set to 22622361 Phenotypes for gene: CFHR5 were set to Nephropathy due to CFHR5 deficiency, MIM# 614809 Review for gene: CFHR5 was set to AMBER