Atypical Haemolytic Uraemic Syndrome_MPGN

Gene: CD46

Green List (high evidence)

Genereviews:
Atypical HUS associated with CD46 pathogenic variants typically presents in childhood with a milder acute episode.
Reports of modifiers leading to a more severe CD46-related aHUS

digenic inheritance has been suggested involving related genes of the complement pathway (PMIDs: 26054645, 26826462).

Created: 11 Apr 2022, 6:29 a.m. | Last Modified: 11 Apr 2022, 6:29 a.m.

Panel Version: 0.12848

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
{Hemolytic uremic syndrome, atypical, susceptibility to, 2} MIM#612922

Publications

• 20301541
• 26054645
• 26826462

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Note: most Path/LP ClinVar entries have removed the ‘susceptibility to’ part of the phenotype.

Atypical hemolytic uremic syndrome 2 (MIM#612922) is usually inherited in a dominant manner, however there are reports of autosomal recessive inheritance where affected individuals presented with earlier onset and more severe symptoms (ClinVar, OMIM). In addition, digenic inheritance has been suggested involving related genes of the complement pathway (PMIDs: 26054645, 26826462). (I)

A number of studies have commented on the fact that disease may be multigenic or rely on additional external factors to develop symptoms...
PMID: 26054645: reviews aHUS disease associated variants, however they note that since penetrance is ~50%, there are probably additional genetic and/or environmental triggers involved.
PMID: 26826462: “Genetic analysis of family members revealed that in most cases the disease develops in individuals with multiple genetic risk factors, which may explain the low penetrance of the mutations.”

Created: 4 Sep 2020, 2:07 a.m. | Last Modified: 4 Sep 2020, 2:07 a.m.

Panel Version: 0.29

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
{Susceptibility to atypical hemolytic uremic syndrome 2} (MIM#612922), AD, AR; Atypical hemolytic uremic syndrome 2

Publications

• PMID: 26054645
• 26826462