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Atypical haemolytic uraemic syndrome v3.10 Eleanor Williams List of related panels changed from R201 to R201; GT997; TP209
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).
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).
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.
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 v3.9 Achchuthan Shanmugasundram Panel version 3.8 has been signed off on 2026-05-06
Atypical haemolytic uraemic syndrome v3.7 Arina Puzriakova Panel version 3.6 has been signed off on 2025-04-30
Atypical haemolytic uraemic syndrome v3.6 ADAMTS13 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: ADAMTS13.
Atypical haemolytic uraemic syndrome v3.6 ADAMTS13 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.

The following is the comment from GMS reviewers:
The testing for associated defects are performed biochemically. The trigger for sequencing of this specific gene is based on clinical MDT and not appropriate as standard practice.
Atypical haemolytic uraemic syndrome v3.6 ADAMTS13 Achchuthan Shanmugasundram changed review comment from: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required before promoting this gene to green.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.
Atypical haemolytic uraemic syndrome v3.6 ADAMTS13 Achchuthan Shanmugasundram commented on gene: ADAMTS13
Atypical haemolytic uraemic syndrome v3.5 ADAMTS13 Achchuthan Shanmugasundram Tag for-review was removed from gene: ADAMTS13.
Atypical haemolytic uraemic syndrome v3.5 Arina Puzriakova Panel version 3.4 has been signed off on 2024-10-30
Atypical haemolytic uraemic syndrome v3.4 Arina Puzriakova Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Atypical haemolytic uraemic syndrome v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Atypical haemolytic uraemic syndrome v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Atypical haemolytic uraemic syndrome v2.17 CFI Achchuthan Shanmugasundram Tag Q2_22_MOI was removed from gene: CFI.
Atypical haemolytic uraemic syndrome v2.17 CFI Achchuthan Shanmugasundram commented on gene: CFI
Atypical haemolytic uraemic syndrome v2.16 CFI Achchuthan Shanmugasundram Mode of inheritance for gene CFI was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Atypical haemolytic uraemic syndrome v2.15 CFI Sarah Leigh Deleted their comment
Atypical haemolytic uraemic syndrome v2.15 CFI Sarah Leigh commented on gene: CFI: Renal insufficiency, glomerulonephritis and pyelonephritis has been reported in Complement factor I deficiency (OMIM:610984)(PMID:17018561; 10352206), therefore it would be appropriate for the mode of inheritance to be changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal in this panel.
Atypical haemolytic uraemic syndrome v2.15 CFI Sarah Leigh Phenotypes for gene: CFI were changed from Hemolytic uremic syndrome, atypical, susceptibility to, 3, OMIM:612923; Complement factor I deficiency, OMIM:610984 to Hemolytic uremic syndrome, atypical, susceptibility to, 3, OMIM:612923; Complement factor I deficiency, OMIM:610984
Atypical haemolytic uraemic syndrome v2.14 CFI Sarah Leigh Phenotypes for gene: CFI were changed from Hemolytic uremic syndrome, atypical, susceptibility to, 3, OMIM:612923; Complement factor I deficiency, OMIM:610984 to Hemolytic uremic syndrome, atypical, susceptibility to, 3, OMIM:612923; Complement factor I deficiency, OMIM:610984
Atypical haemolytic uraemic syndrome v2.13 CFI Sarah Leigh Phenotypes for gene: CFI were changed from Hemolytic uremic syndrome, atypical, susceptibility to, 3, OMIM:612923 to Hemolytic uremic syndrome, atypical, susceptibility to, 3, OMIM:612923; Complement factor I deficiency, OMIM:610984
Atypical haemolytic uraemic syndrome v2.12 CFI Sarah Leigh Publications for gene: CFI were set to 16621965; 17597211; 15173250; 23685748
Atypical haemolytic uraemic syndrome v2.11 CFI Sarah Leigh edited their review of gene: CFI: Added comment: Renal insufficiency, glomerulonephritis and pyelonephritis has been reported in Complement factor I deficiency (OMIM:610984)(PMID:17018561; 10352206), therefore it would be appropriate for the mode of inheritance to be changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal in this panel.; Changed publications to: 17018561, 10352206; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Atypical haemolytic uraemic syndrome v2.11 CFI Sarah Leigh Tag Q2_22_MOI tag was added to gene: CFI.
Atypical haemolytic uraemic syndrome v2.11 CFI Sarah Leigh Phenotypes for gene: CFI were changed from Hemolytic uremic syndrome, atypical, susceptibility to, 3 612923 to Hemolytic uremic syndrome, atypical, susceptibility to, 3, OMIM:612923
Atypical haemolytic uraemic syndrome v2.10 ADAMTS13 Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: ADAMTS13.
Atypical haemolytic uraemic syndrome v2.10 CFB Eleanor Williams Added comment: Comment on mode of inheritance: In OMIM this gene is also provisionally associated with Complement factor B deficiency based on evidence from one family with biallelic variants in CFB. However, given the phenotype/level of evidence it is not appropriate to change the mode of inheritance to Both monoallelic and biallelic on this panel.
Atypical haemolytic uraemic syndrome v2.10 CFB Eleanor Williams Mode of inheritance for gene: CFB was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Atypical haemolytic uraemic syndrome v2.9 C3 Ivone Leong Phenotypes for gene: C3 were changed from Hemolytic uremic syndrome, atypical, susceptibility to, 5, 612925 to Hemolytic uremic syndrome, atypical, susceptibility to, 5, OMIM:612925
Atypical haemolytic uraemic syndrome v2.8 ADAMTS13 Arina Puzriakova Phenotypes for gene: ADAMTS13 were changed from Thrombotic thrombocytopenic purpura, familial, MIM# 274150 to Thrombotic thrombocytopenic purpura, hereditary, OMIM:274150
Atypical haemolytic uraemic syndrome v2.7 ADAMTS13 Eleanor Williams Tag for-review tag was added to gene: ADAMTS13.
Atypical haemolytic uraemic syndrome v2.7 ADAMTS13 Eleanor Williams Publications for gene: ADAMTS13 were set to
Atypical haemolytic uraemic syndrome v2.6 ADAMTS13 Eleanor Williams Classified gene: ADAMTS13 as Amber List (moderate evidence)
Atypical haemolytic uraemic syndrome v2.6 ADAMTS13 Eleanor Williams Gene: adamts13 has been classified as Amber List (Moderate Evidence).
Atypical haemolytic uraemic syndrome v2.5 ADAMTS13 Eleanor Williams commented on gene: ADAMTS13: Associated with Thrombotic thrombocytopenic purpura, hereditary #274150 (AR) in OMIM.

After consultation with the Genomics England clinical team it was decided to add this gene as Amber and discuss with the GMS group at the next update. ADAMTS13 may be responsible for a mimic of aHUS, that might be difficult to distinguish clinically. Therefore it is possible that inclusion in a differential diagnosis capacity is relevant.
Atypical haemolytic uraemic syndrome v2.5 ADAMTS13 Eleanor Williams changed review comment from: Consulting with the Genomics England clinical team as to whether to add this gene to the panel.; to: Consulting with the Genomics England clinical team as to whether to add this gene to the panel.
Atypical haemolytic uraemic syndrome v2.5 CFHR5 Eleanor Williams Classified gene: CFHR5 as Amber List (moderate evidence)
Atypical haemolytic uraemic syndrome v2.5 CFHR5 Eleanor Williams Added comment: 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
Atypical haemolytic uraemic syndrome v2.5 CFHR5 Eleanor Williams Gene: cfhr5 has been classified as Amber List (Moderate Evidence).
Atypical haemolytic uraemic syndrome v2.4 CFHR5 Eleanor Williams Publications for gene: CFHR5 were set to 22622361
Atypical haemolytic uraemic syndrome v2.3 Eleanor Williams Panel version has been signed off
Atypical haemolytic uraemic syndrome v2.2 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; GMS signed-off
Atypical haemolytic uraemic syndrome v2.1 CFHR5 Eleanor Williams reviewed gene: CFHR5: Rating: AMBER; Mode of pathogenicity: None; Publications: 20513133, 22622361, 30905589, 29500241; Phenotypes: ; Mode of inheritance: None
Atypical haemolytic uraemic syndrome v2.1 ADAMTS13 Eleanor Williams commented on gene: ADAMTS13
Atypical haemolytic uraemic syndrome v2.1 CFHR5 Zornitza Stark 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
Added comment: There is at least one paper specifically linking variants in this gene with aHUS, not quite sure where this gene belongs.
Sources: Expert list
Atypical haemolytic uraemic syndrome v2.1 ADAMTS13 Zornitza Stark gene: ADAMTS13 was added
gene: ADAMTS13 was added to Atypical haemolytic uraemic syndrome. Sources: Expert list
Mode of inheritance for gene: ADAMTS13 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ADAMTS13 were set to Thrombotic thrombocytopenic purpura, familial, MIM# 274150
Review for gene: ADAMTS13 was set to AMBER
Added comment: It is difficult to know whether to include this gene on an aHUS panel; there is considerable overlap in the clinical features between TTP and HUS, and we have included it in ours.
Sources: Expert list
Atypical haemolytic uraemic syndrome v2.0 Ellen McDonagh promoted panel to version 2.0
Atypical haemolytic uraemic syndrome v1.22 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease; GMS signed-off
Atypical haemolytic uraemic syndrome v1.21 Eleanor Williams List of related panels changed from to R201
Atypical haemolytic uraemic syndrome v1.20 THBD Eleanor Williams Phenotypes for gene: THBD were changed from Hemolytic uremic syndrome, atypical, susceptibility to, 6, 612926 to Hemolytic uremic syndrome, atypical, susceptibility to, 6, 612926; Thrombophilia due to thrombomodulin defect 614486
Atypical haemolytic uraemic syndrome v1.19 VTN Eleanor Williams Phenotypes for gene: VTN were changed from to Atypical haemolytic uraemic syndrome; aHUS
Atypical haemolytic uraemic syndrome v1.18 VTN Eleanor Williams Publications for gene: VTN were set to
Atypical haemolytic uraemic syndrome v1.17 VTN Eleanor Williams Mode of inheritance for gene: VTN was changed from to Unknown
Atypical haemolytic uraemic syndrome v1.16 INF2 Eleanor Williams Phenotypes for gene: INF2 were changed from to Charcot-Marie-Tooth disease, dominant intermediate E, 614455; Glomerulosclerosis, focal segmental, 5, 613237
Atypical haemolytic uraemic syndrome v1.15 INF2 Eleanor Williams Publications for gene: INF2 were set to
Atypical haemolytic uraemic syndrome v1.14 INF2 Eleanor Williams Mode of inheritance for gene: INF2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Atypical haemolytic uraemic syndrome v1.13 MMACHC Eleanor Williams changed review comment from: PMID: 29068997 - Chen et al 2017 - 4-year-old girl with a diagnosis of aHUS. Genetic analysis revealed a compound heterozygous MMACHC mutation exonl: c. 80A >G, c. 609G >A. After treated by vitamin B12 for 10 days, the patient condition significantly improved. Note: her healthy younger sister also had both mutations. Her parents each had one of the variants.

PMID: 27324188 - Adrovic et al 2016 - describe the case of a 6-year-old girl with cblC disorder, who presented with severe multiorgan involvement at the age of 5 months and who was successfully treated with vitamin B12, betaine, coenzyme Q10 and l-carnitene, and who had a new homozygous mutation of MMACHC c. 484G > T, p.Gly162Trp

PMID: 24210589 - Cornec-Le Gall et al 2014 - Abstract only accessed. Describe a patient with atypical hemolytic uremic syndrome that did not respond to eculizumab. Very low plasma methionine levels associated with methylmalonic aciduria, which suggested cobalamin C disease. MMACHC sequencing revealed compound heterozygosity for 2 causative mutations.

PMID: 17874135 - Sharma et al 2007 - report a child diagnosed with Diarrhea-negative HUS secondary to cblC disease in infancy. Mutation analysis in this patient identified homozygosity for the 271 dupA mutation (c.271 dupA) in the cblC MMACHC gene.

PMID: 12210350 - Van Hove et al 2002 - Abstract only accessed. Report 2 siblings,with proteinuria and hematuria, hypertension, and chronic hemolytic anemia. Both patients had hyperhomocysteinemia and mild methylmalonic aciduria. Both patients and their father carry a balanced reciprocal translocation but the abstract does not state where in the genome this is.

PMID: 1593355 - Geraghty et al 1992 - Abstract only accessed. Describe a female infant with typical features of the cobalamin C form of combined methylmalonic aciduria and homocystinuria who also had the hemolytic-uremic syndrome with thrombocytopenia, microangiopathic hemolytic anemia, hypertension, and renal failure. No sequencing of the gene reported in the abstract.

PMID: 11972107 - Kind et al 2002 - a case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS) in the neonatal period is described. No sequencing of the gene reported.; to: Associated with Methylmalonic aciduria and homocystinuria, cblC type (#277400) in OMIM.

PMID: 29068997 - Chen et al 2017 - 4-year-old girl with a diagnosis of aHUS. Genetic analysis revealed a compound heterozygous MMACHC mutation exonl: c. 80A >G, c. 609G >A. After treated by vitamin B12 for 10 days, the patient condition significantly improved. Note: her healthy younger sister also had both mutations. Her parents each had one of the variants.

PMID: 27324188 - Adrovic et al 2016 - describe the case of a 6-year-old girl with cblC disorder, who presented with severe multiorgan involvement at the age of 5 months and who was successfully treated with vitamin B12, betaine, coenzyme Q10 and l-carnitene, and who had a new homozygous mutation of MMACHC c. 484G > T, p.Gly162Trp

PMID: 24210589 - Cornec-Le Gall et al 2014 - Abstract only accessed. Describe a patient with atypical hemolytic uremic syndrome that did not respond to eculizumab. Very low plasma methionine levels associated with methylmalonic aciduria, which suggested cobalamin C disease. MMACHC sequencing revealed compound heterozygosity for 2 causative mutations.

PMID: 17874135 - Sharma et al 2007 - report a child diagnosed with Diarrhea-negative HUS secondary to cblC disease in infancy. Mutation analysis in this patient identified homozygosity for the 271 dupA mutation (c.271 dupA) in the cblC MMACHC gene.

PMID: 12210350 - Van Hove et al 2002 - Abstract only accessed. Report 2 siblings,with proteinuria and hematuria, hypertension, and chronic hemolytic anemia. Both patients had hyperhomocysteinemia and mild methylmalonic aciduria. Both patients and their father carry a balanced reciprocal translocation but the abstract does not state where in the genome this is.

PMID: 1593355 - Geraghty et al 1992 - Abstract only accessed. Describe a female infant with typical features of the cobalamin C form of combined methylmalonic aciduria and homocystinuria who also had the hemolytic-uremic syndrome with thrombocytopenia, microangiopathic hemolytic anemia, hypertension, and renal failure. No sequencing of the gene reported in the abstract.

PMID: 11972107 - Kind et al 2002 - a case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS) in the neonatal period is described. No sequencing of the gene reported.
Atypical haemolytic uraemic syndrome v1.13 MMACHC Eleanor Williams Phenotypes for gene: MMACHC were changed from to Methylmalonic aciduria and homocystinuria, cblC type, 277400
Atypical haemolytic uraemic syndrome v1.12 MMACHC Eleanor Williams Publications for gene: MMACHC were set to
Atypical haemolytic uraemic syndrome v1.11 MMACHC Eleanor Williams Mode of inheritance for gene: MMACHC was changed from to BIALLELIC, autosomal or pseudoautosomal
Atypical haemolytic uraemic syndrome v1.10 MMACHC Eleanor Williams Classified gene: MMACHC as Green List (high evidence)
Atypical haemolytic uraemic syndrome v1.10 MMACHC Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. More than 3 cases, with different variants reported, although in one case the healthy sister also had the same variants as the proband.
Atypical haemolytic uraemic syndrome v1.10 MMACHC Eleanor Williams Gene: mmachc has been classified as Green List (High Evidence).
Atypical haemolytic uraemic syndrome v1.9 MMACHC Eleanor Williams changed review comment from: PMID: 29068997 - Chen et al 2017 - 4-year-old girl with a diagnosis of aHUS. Genetic analysis revealed a compound heterozygous MMACHC mutation exonl: c. 80A >G, c. 609G >A. After treated by vitamin B12 for 10 days, the patient condition significantly improved. Note: her healthy younger sister also had both mutations. Her parents each had one of the variants.

PMID: 27324188 - Adrovic et al 2016 - describe the case of a 6-year-old girl with cblC disorder, who presented with severe multiorgan involvement at the age of 5 months and who was successfully treated with vitamin B12, betaine, coenzyme Q10 and l-carnitene, and who had a new homozygous mutation of MMACHC c. 484G > T, p.Gly162Trp

PMID: 24210589 - Cornec-Le Gall et al 2014 - Abstract only accessed. Describe a patient with atypical hemolytic uremic syndrome that did not respond to eculizumab. Very low plasma methionine levels associated with methylmalonic aciduria, which suggested cobalamin C disease. MMACHC sequencing revealed compound heterozygosity for 2 causative mutations.

PMID: 12210350 - Van Hove et al 2002 - Abstract only accessed. Report 2 siblings,with proteinuria and hematuria, hypertension, and chronic hemolytic anemia. Both patients had hyperhomocysteinemia and mild methylmalonic aciduria. Both patients and their father carry a balanced reciprocal translocation but the abstract does not state where in the genome this is.

PMID: 17874135 - Sharma et al 2007 - report a child diagnosed with Diarrhea-negative HUS secondary to cblC disease in infancy. Mutation analysis in this patient identified homozygosity for the 271 dupA mutation (c.271 dupA) in the cblC MMACHC gene.

PMID: 1593355 - Geraghty et al 1992 - Abstract only accessed. Describe a female infant with typical features of the cobalamin C form of combined methylmalonic aciduria and homocystinuria who also had the hemolytic-uremic syndrome with thrombocytopenia, microangiopathic hemolytic anemia, hypertension, and renal failure. No sequencing of the gene reported in the abstract.

PMID: 11972107 - Kind et al 2002 - a case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS) in the neonatal period is described. No sequencing of the gene reported.; to: PMID: 29068997 - Chen et al 2017 - 4-year-old girl with a diagnosis of aHUS. Genetic analysis revealed a compound heterozygous MMACHC mutation exonl: c. 80A >G, c. 609G >A. After treated by vitamin B12 for 10 days, the patient condition significantly improved. Note: her healthy younger sister also had both mutations. Her parents each had one of the variants.

PMID: 27324188 - Adrovic et al 2016 - describe the case of a 6-year-old girl with cblC disorder, who presented with severe multiorgan involvement at the age of 5 months and who was successfully treated with vitamin B12, betaine, coenzyme Q10 and l-carnitene, and who had a new homozygous mutation of MMACHC c. 484G > T, p.Gly162Trp

PMID: 24210589 - Cornec-Le Gall et al 2014 - Abstract only accessed. Describe a patient with atypical hemolytic uremic syndrome that did not respond to eculizumab. Very low plasma methionine levels associated with methylmalonic aciduria, which suggested cobalamin C disease. MMACHC sequencing revealed compound heterozygosity for 2 causative mutations.

PMID: 17874135 - Sharma et al 2007 - report a child diagnosed with Diarrhea-negative HUS secondary to cblC disease in infancy. Mutation analysis in this patient identified homozygosity for the 271 dupA mutation (c.271 dupA) in the cblC MMACHC gene.

PMID: 12210350 - Van Hove et al 2002 - Abstract only accessed. Report 2 siblings,with proteinuria and hematuria, hypertension, and chronic hemolytic anemia. Both patients had hyperhomocysteinemia and mild methylmalonic aciduria. Both patients and their father carry a balanced reciprocal translocation but the abstract does not state where in the genome this is.

PMID: 1593355 - Geraghty et al 1992 - Abstract only accessed. Describe a female infant with typical features of the cobalamin C form of combined methylmalonic aciduria and homocystinuria who also had the hemolytic-uremic syndrome with thrombocytopenia, microangiopathic hemolytic anemia, hypertension, and renal failure. No sequencing of the gene reported in the abstract.

PMID: 11972107 - Kind et al 2002 - a case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS) in the neonatal period is described. No sequencing of the gene reported.
Atypical haemolytic uraemic syndrome v1.9 MMACHC Eleanor Williams commented on gene: MMACHC: PMID: 29068997 - Chen et al 2017 - 4-year-old girl with a diagnosis of aHUS. Genetic analysis revealed a compound heterozygous MMACHC mutation exonl: c. 80A >G, c. 609G >A. After treated by vitamin B12 for 10 days, the patient condition significantly improved. Note: her healthy younger sister also had both mutations. Her parents each had one of the variants.

PMID: 27324188 - Adrovic et al 2016 - describe the case of a 6-year-old girl with cblC disorder, who presented with severe multiorgan involvement at the age of 5 months and who was successfully treated with vitamin B12, betaine, coenzyme Q10 and l-carnitene, and who had a new homozygous mutation of MMACHC c. 484G > T, p.Gly162Trp

PMID: 24210589 - Cornec-Le Gall et al 2014 - Abstract only accessed. Describe a patient with atypical hemolytic uremic syndrome that did not respond to eculizumab. Very low plasma methionine levels associated with methylmalonic aciduria, which suggested cobalamin C disease. MMACHC sequencing revealed compound heterozygosity for 2 causative mutations.

PMID: 12210350 - Van Hove et al 2002 - Abstract only accessed. Report 2 siblings,with proteinuria and hematuria, hypertension, and chronic hemolytic anemia. Both patients had hyperhomocysteinemia and mild methylmalonic aciduria. Both patients and their father carry a balanced reciprocal translocation but the abstract does not state where in the genome this is.

PMID: 17874135 - Sharma et al 2007 - report a child diagnosed with Diarrhea-negative HUS secondary to cblC disease in infancy. Mutation analysis in this patient identified homozygosity for the 271 dupA mutation (c.271 dupA) in the cblC MMACHC gene.

PMID: 1593355 - Geraghty et al 1992 - Abstract only accessed. Describe a female infant with typical features of the cobalamin C form of combined methylmalonic aciduria and homocystinuria who also had the hemolytic-uremic syndrome with thrombocytopenia, microangiopathic hemolytic anemia, hypertension, and renal failure. No sequencing of the gene reported in the abstract.

PMID: 11972107 - Kind et al 2002 - a case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS) in the neonatal period is described. No sequencing of the gene reported.
Atypical haemolytic uraemic syndrome v1.9 CFHR4 David Kavanagh reviewed gene: CFHR4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
Atypical haemolytic uraemic syndrome v1.9 THBD David Kavanagh reviewed gene: THBD: Rating: RED; Mode of pathogenicity: None; Publications: 19625716; Phenotypes: Thrombophilia due to thrombomodulin defect MIM614486, aHUS MIMN 612926; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Atypical haemolytic uraemic syndrome v1.9 VTN David Kavanagh reviewed gene: VTN: Rating: RED; Mode of pathogenicity: None; Publications: 30377230; Phenotypes: aHUS; Mode of inheritance: Unknown
Atypical haemolytic uraemic syndrome v1.9 INF2 David Kavanagh reviewed gene: INF2: Rating: RED; Mode of pathogenicity: None; Publications: 27974406; Phenotypes: FSGS MIM 613237, CHT MIM 614455; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Atypical haemolytic uraemic syndrome v1.9 MMACHC David Kavanagh reviewed gene: MMACHC: Rating: GREEN; Mode of pathogenicity: None; Publications: 24210589, 1593355, 11972107, 12210350, 17874135; Phenotypes: OMIM 277400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Atypical haemolytic uraemic syndrome v1.7 THBD Eleanor Williams commented on gene: THBD: THBD was discussed on the NHS GMS renal specialist group call on 2019-02-04. It was decided that this gene should remain red on the panel.
Atypical haemolytic uraemic syndrome v1.7 THBD Eleanor Williams reviewed gene: THBD: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Atypical haemolytic uraemic syndrome v1.7 INF2 Eleanor Williams reviewed gene: INF2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Atypical haemolytic uraemic syndrome v1.7 MMACHC Eleanor Williams reviewed gene: MMACHC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Atypical haemolytic uraemic syndrome v1.7 VTN Eleanor Williams reviewed gene: VTN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Atypical haemolytic uraemic syndrome v1.7 DGKE Eleanor Williams reviewed gene: DGKE: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Atypical haemolytic uraemic syndrome v1.7 CFHR1 Eleanor Williams reviewed gene: CFHR1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Atypical haemolytic uraemic syndrome v1.7 CFB Eleanor Williams reviewed gene: CFB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Atypical haemolytic uraemic syndrome v1.7 C3 Eleanor Williams reviewed gene: C3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
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 v1.7 CFI Eleanor Williams reviewed gene: CFI: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Atypical haemolytic uraemic syndrome v1.7 CFH Eleanor Williams reviewed gene: CFH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Atypical haemolytic uraemic syndrome v1.6 THBD Eleanor Williams Source NHS GMS was added to THBD.
Atypical haemolytic uraemic syndrome v1.6 INF2 Eleanor Williams gene: INF2 was added
gene: INF2 was added to Atypical haemolytic uraemic syndrome. Sources: NHS GMS
Mode of inheritance for gene: INF2 was set to
Atypical haemolytic uraemic syndrome v1.6 MMACHC Eleanor Williams gene: MMACHC was added
gene: MMACHC was added to Atypical haemolytic uraemic syndrome. Sources: NHS GMS
Mode of inheritance for gene: MMACHC was set to
Atypical haemolytic uraemic syndrome v1.6 VTN Eleanor Williams gene: VTN was added
gene: VTN was added to Atypical haemolytic uraemic syndrome. Sources: NHS GMS
Mode of inheritance for gene: VTN was set to
Atypical haemolytic uraemic syndrome v1.6 DGKE Eleanor Williams Source NHS GMS was added to DGKE.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Atypical haemolytic uraemic syndrome v1.6 CFHR1 Eleanor Williams Source NHS GMS was added to CFHR1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Atypical haemolytic uraemic syndrome v1.6 CFB Eleanor Williams Source NHS GMS was added to CFB.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Atypical haemolytic uraemic syndrome v1.6 C3 Eleanor Williams Source NHS GMS was added to C3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
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)
Atypical haemolytic uraemic syndrome v1.6 CFI Eleanor Williams Source NHS GMS was added to CFI.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Atypical haemolytic uraemic syndrome v1.6 CFH Eleanor Williams Source NHS GMS was added to CFH.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Atypical haemolytic uraemic syndrome v1.4 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease
Atypical haemolytic uraemic syndrome THBD Louise Daugherty reviewed gene: THBD
Atypical haemolytic uraemic syndrome CFHR4 Louise Daugherty Added gene to panel
Atypical haemolytic uraemic syndrome Sarah Leigh promoted panel to version 1
Atypical haemolytic uraemic syndrome THBD Sarah Leigh marked THBD as ready
Atypical haemolytic uraemic syndrome THBD Sarah Leigh classified THBD as red
Atypical haemolytic uraemic syndrome DGKE Sarah Leigh marked DGKE as ready
Atypical haemolytic uraemic syndrome DGKE Sarah Leigh classified DGKE as green
Atypical haemolytic uraemic syndrome DGKE Sarah Leigh added DGKE to panel
Atypical haemolytic uraemic syndrome DGKE Sarah Leigh reviewed DGKE
Atypical haemolytic uraemic syndrome THBD Sarah Leigh edited their review of THBD
Atypical haemolytic uraemic syndrome THBD Sarah Leigh commented on THBD
Atypical haemolytic uraemic syndrome CFB Sarah Leigh marked CFB as ready
Atypical haemolytic uraemic syndrome CFB Sarah Leigh classified CFB as green
Atypical haemolytic uraemic syndrome CFB Sarah Leigh commented on CFB
Atypical haemolytic uraemic syndrome C3 Sarah Leigh classified C3 as green
Atypical haemolytic uraemic syndrome C3 Sarah Leigh marked C3 as ready
Atypical haemolytic uraemic syndrome C3 Sarah Leigh commented on C3
Atypical haemolytic uraemic syndrome CFI Sarah Leigh marked CFI as ready
Atypical haemolytic uraemic syndrome CFI Sarah Leigh commented on CFI
Atypical haemolytic uraemic syndrome CFH Sarah Leigh marked CFH as ready
Atypical haemolytic uraemic syndrome CFH Sarah Leigh commented on CFH
Atypical haemolytic uraemic syndrome CFHR1 Sarah Leigh marked CFHR1 as ready
Atypical haemolytic uraemic syndrome CFHR1 Sarah Leigh classified CFHR1 as green
Atypical haemolytic uraemic syndrome CFHR1 Sarah Leigh added CFHR1 to panel
Atypical haemolytic uraemic syndrome CFHR1 Sarah Leigh reviewed CFHR1
Atypical haemolytic uraemic syndrome CFHR3 Sarah Leigh classified CFHR3 as green
Atypical haemolytic uraemic syndrome CFHR3 Sarah Leigh marked CFHR3 as ready
Atypical haemolytic uraemic syndrome CFHR3 Sarah Leigh added CFHR3 to panel
Atypical haemolytic uraemic syndrome CFHR3 Sarah Leigh reviewed CFHR3
Atypical haemolytic uraemic syndrome CD46 Sarah Leigh marked CD46 as ready
Atypical haemolytic uraemic syndrome CD46 Sarah Leigh commented on CD46