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| Atypical haemolytic uraemic syndrome v3.9 | CD46 | Ida Ertmanska edited their review of gene: CD46: Changed rating: GREEN; Changed publications to: 14566051, 29644059, 33238263, 33224962, 34169201, 38317858, 40983966; Changed phenotypes to: {Hemolytic uremic syndrome, atypical, susceptibility to, 2}, OMIM:612922; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Atypical haemolytic uraemic syndrome v3.9 | CD46 |
Ida Ertmanska changed review comment from: PMID: 40983966 Hu et al., 2025 Case of a 27-year-old Chinese male diagnosed with atypical Hemolytic Uremic Syndrome (aHUS) at the age of 8, who has experienced seven relapses over a span of 19 years. He was homozygous for a mutation in CD46: c.1127+2T>A (WES). CD46 mRNA and protein expression in the patient's peripheral blood were significantly reduced. PMID: 38317858 Al Riyami et al., 2023 Patient 5 - Omani ancestry - diagnosed with aHUS, heterozygous for CD46 c.175C>T, p.Arg59* (classified Pathogenic / suscept allele) and also het for CFH c.965-6T>C (VUS). PMID: 34169201 Ardissino et al., 2021 Study highlights low penetrance: 2/32 carriers of CD46 mutations (from 16 different families) actually developed aHUS. Two affected carriers harboured CD46 c.98-1G>C and c.286+2T>G splice variants, both classified as LP - second variant also found in 4 healthy family members. Of all 186 individuals with a complement gene abnormality, only 28 developed aHUS - not CD46 specific. PMID: 33224962 Piras et al., 2020 Studied 485 aHUS patients and found CD46 rare variants (RVs) in about 10%. The c.286+2T>G was the most prevalent (13/485) and was associated with <30% penetrance. Reported a large pedigree including a proband het for CD46 c.286+2T>G with severe aHUS and developed end-stage renal failure. The father and paternal uncle with the same variant in homozygosity and six heterozygous relatives are unaffected. Flow cytometry showed about 50% reduction of CD46 expression on blood mononuclear cells from the het proband and over 90% reduction in cells from the proband's unaffected homozygous father and aunt - highlights complexity of aHUS, and that CD46 deficiency may not be enough to induce aHUS. CD46 is associated with AD,AR {Hemolytic uremic syndrome, atypical, susceptibility to, 2}, OMIM:612922 (OMIM accessed 24th Jun 2026). The association between CD46 and semi-dominant atypical hemolytic-uremic syndrome is also classified as Definitive in ClinGen (Complement-Mediated Kidney Diseases GCEP, June 2024).; to: BIALLELIC CASES: PMID: 40983966 Hu et al., 2025 Case of a 27-year-old Chinese male diagnosed with atypical Hemolytic Uremic Syndrome (aHUS) at the age of 8, who has experienced seven relapses over a span of 19 years. He was homozygous for a mutation in CD46: c.1127+2T>A (WES). CD46 mRNA and protein expression in the patient's peripheral blood were significantly reduced. Other modifier mutations may affect penetrance here. PMID: 33238263 Bamhraz et al., 2020 Saudi Arabian aHUS cohort. Patient 1 homozygous for CD46: c.736T>A (p.Phe246Ile) variant, as well as het for CFI c.540A>G (p.Glu180Glu) - both labelled VUS. Disease onset at 10yrs, complete recovery after eculizumab treatment. Patient 5 - homozygous for CD46: c.769 C>A (p.Cys 256*) - LP, as well as heterozygous for CFI c.803 C>T (p.Ser268Leu) variant (LB). Disease onset at 2.5yrs, developed into ESRD and required a post-kidney transplant. Patient 7 - homozygous for CD46: c.350-351dup AC (p.Glu11ThfsX17) - LP. Disease onset at 21 months. Patient responded to plasma therapy leading to full recovery. PMID: 29644059 Khandelwal et al., 2018 Cohort of Indian children with aHUS. Sibling pairs 2–3 and 7–8 with familial disease showed a homozygous c.286 + 2T > G splice-site mutation; in both families, the parents were consanguineous. Patient 9 had a homozygous c.104G > A, p.Cys35Tyr; his affected sibling had died before genetic evaluation. 3 unrelated families total. PMID: 14566051 Richards et al., 2003 Family 3 - recessive aHUS, CD46 c.822T>C, p.Ser206Pro. Same mutation caused aHUS in Family 2 in a heterozygous state. Demonstrated that het patients had protein expression reduced by 50%, and it was absent in homozygotes. MONOALLELIC: PMID: 38317858 Al Riyami et al., 2023 Patient 5 - Omani ancestry - diagnosed with aHUS, heterozygous for CD46 c.175C>T, p.Arg59* (classified Pathogenic / suscept allele) and also het for CFH c.965-6T>C (VUS). PMID: 34169201 Ardissino et al., 2021 Study highlights low penetrance: 2/32 carriers of CD46 mutations (from 16 different families) actually developed aHUS. Two affected carriers harboured CD46 c.98-1G>C and c.286+2T>G splice variants, both classified as LP - second variant also found in 4 healthy family members. Of all 186 individuals with a complement gene abnormality, only 28 developed aHUS - not CD46 specific. PMID: 33224962 Piras et al., 2020 Studied 485 aHUS patients and found CD46 rare variants (RVs) in about 10%. The c.286+2T>G was the most prevalent (13/485) and was associated with <30% penetrance. Reported a large pedigree including a proband het for CD46 c.286+2T>G with severe aHUS and developed end-stage renal failure. The father and paternal uncle with the same variant in homozygosity and six het relatives are unaffected. Flow cytometry showed about 50% reduction of CD46 expression on blood mononuclear cells from the het proband and over 90% reduction in cells from the proband's unaffected homozygous father and aunt - highlights complexity of aHUS, and that CD46 deficiency may not be enough to induce aHUS. CD46 is associated with AD,AR {Hemolytic uremic syndrome, atypical, susceptibility to, 2}, OMIM:612922 (OMIM accessed 24th Jun 2026). The association between CD46 and semi-dominant atypical hemolytic-uremic syndrome is also classified as Definitive in ClinGen (Complement-Mediated Kidney Diseases GCEP, June 2024). |
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| Atypical haemolytic uraemic syndrome v3.9 | CD46 |
Ida Ertmanska changed review comment from: PMID: 40983966 Hu et al., 2025 Case of a 27-year-old Chinese male diagnosed with atypical Hemolytic Uremic Syndrome (aHUS) at the age of 8, who has experienced seven relapses over a span of 19 years. He was homozygous for a mutation in CD46: c.1127+2T>A (WES). CD46 mRNA and protein expression in the patient's peripheral blood were significantly reduced. PMID: 33224962 Piras et al., 2020 Studied 485 aHUS patients and found CD46 rare variants (RVs) in about 10%. The c.286+2T>G was the most prevalent (13/485) and was associated with <30% penetrance. Reported a large pedigree including a proband het for CD46 c.286+2T>G with severe aHUS and developed end-stage renal failure. The father and paternal uncle with the same variant in homozygosity and six heterozygous relatives are unaffected. Flow cytometry showed about 50% reduction of CD46 expression on blood mononuclear cells from the het proband and over 90% reduction in cells from the proband's unaffected homozygous father and aunt - highlights complexity of aHUS, and that CD46 deficiency may not be enough to induce aHUS.; to: PMID: 40983966 Hu et al., 2025 Case of a 27-year-old Chinese male diagnosed with atypical Hemolytic Uremic Syndrome (aHUS) at the age of 8, who has experienced seven relapses over a span of 19 years. He was homozygous for a mutation in CD46: c.1127+2T>A (WES). CD46 mRNA and protein expression in the patient's peripheral blood were significantly reduced. PMID: 38317858 Al Riyami et al., 2023 Patient 5 - Omani ancestry - diagnosed with aHUS, heterozygous for CD46 c.175C>T, p.Arg59* (classified Pathogenic / suscept allele) and also het for CFH c.965-6T>C (VUS). PMID: 34169201 Ardissino et al., 2021 Study highlights low penetrance: 2/32 carriers of CD46 mutations (from 16 different families) actually developed aHUS. Two affected carriers harboured CD46 c.98-1G>C and c.286+2T>G splice variants, both classified as LP - second variant also found in 4 healthy family members. Of all 186 individuals with a complement gene abnormality, only 28 developed aHUS - not CD46 specific. PMID: 33224962 Piras et al., 2020 Studied 485 aHUS patients and found CD46 rare variants (RVs) in about 10%. The c.286+2T>G was the most prevalent (13/485) and was associated with <30% penetrance. Reported a large pedigree including a proband het for CD46 c.286+2T>G with severe aHUS and developed end-stage renal failure. The father and paternal uncle with the same variant in homozygosity and six heterozygous relatives are unaffected. Flow cytometry showed about 50% reduction of CD46 expression on blood mononuclear cells from the het proband and over 90% reduction in cells from the proband's unaffected homozygous father and aunt - highlights complexity of aHUS, and that CD46 deficiency may not be enough to induce aHUS. CD46 is associated with AD,AR {Hemolytic uremic syndrome, atypical, susceptibility to, 2}, OMIM:612922 (OMIM accessed 24th Jun 2026). The association between CD46 and semi-dominant atypical hemolytic-uremic syndrome is also classified as Definitive in ClinGen (Complement-Mediated Kidney Diseases GCEP, June 2024). |
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| Atypical haemolytic uraemic syndrome v3.9 | CD46 |
Ida Ertmanska changed review comment from: PMID: 40983966 Hu et al., 2025 Case of a 27-year-old Chinese male diagnosed with atypical Hemolytic Uremic Syndrome (aHUS) at the age of 8, who has experienced seven relapses over a span of 19 years. He was homozygous for a mutation in CD46: c.1127+2T>A (WES). CD46 mRNA and protein expression in the patient's peripheral blood were significantly reduced. PMID: 33224962 Piras et al., 2020 Studied 485 aHUS patients and found CD46 rare variants (RVs) in about 10%. The c.286+2T>G RV was the most prevalent (13/485) and was associated with <30% penetrance. Reported a large pedigree including a proband het for CD46 c.286+2T>G with severe aHUS and developed end-stage renal failure. The father and paternal uncle with the same variant in homozygosity and six heterozygous relatives are unaffected. Flow cytometry showed about 50% reduction of CD46 expression on blood mononuclear cells from the het proband and over 90% reduction in cells from the proband's unaffected homozygous father and aunt - highlights complexity of aHUS, and that CD46 deficiency may not be enough to induce aHUS.; to: PMID: 40983966 Hu et al., 2025 Case of a 27-year-old Chinese male diagnosed with atypical Hemolytic Uremic Syndrome (aHUS) at the age of 8, who has experienced seven relapses over a span of 19 years. He was homozygous for a mutation in CD46: c.1127+2T>A (WES). CD46 mRNA and protein expression in the patient's peripheral blood were significantly reduced. PMID: 33224962 Piras et al., 2020 Studied 485 aHUS patients and found CD46 rare variants (RVs) in about 10%. The c.286+2T>G was the most prevalent (13/485) and was associated with <30% penetrance. Reported a large pedigree including a proband het for CD46 c.286+2T>G with severe aHUS and developed end-stage renal failure. The father and paternal uncle with the same variant in homozygosity and six heterozygous relatives are unaffected. Flow cytometry showed about 50% reduction of CD46 expression on blood mononuclear cells from the het proband and over 90% reduction in cells from the proband's unaffected homozygous father and aunt - highlights complexity of aHUS, and that CD46 deficiency may not be enough to induce aHUS. |
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| Atypical haemolytic uraemic syndrome v3.9 | CD46 | Ida Ertmanska reviewed gene: CD46: Rating: ; Mode of pathogenicity: None; Publications: 33224962, 40983966; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Atypical haemolytic uraemic syndrome v1.7 | CD46 | Eleanor Williams reviewed gene: CD46: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Atypical haemolytic uraemic syndrome v1.6 | CD46 |
Eleanor Williams Source NHS GMS was added to CD46. Rating Changed from Green List (high evidence) to Green List (high evidence) |
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| Atypical haemolytic uraemic syndrome | CD46 | Sarah Leigh marked CD46 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Atypical haemolytic uraemic syndrome | CD46 | Sarah Leigh commented on CD46 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||