Combined Immunodeficiency

Gene: MTHFD1

Green List (high evidence)

MTHFD1 (methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1)
EnsemblGeneIds (GRCh38): ENSG00000100714
EnsemblGeneIds (GRCh37): ENSG00000100714
OMIM: 172460, Gene2Phenotype
MTHFD1 is in 6 panels

1 review

Danielle Ariti (University of Melbourne)

Green List (high evidence)

8 individuals from 4 unrelated families have been reported; multiple mouse models

7 individuals were Compound heterozygous (nonsense & missense) and 1 was homozygous (missense) for MTHFD1 variants often resulting in alteration of highly conserved residues in binding-sites.

Individuals typically present with megaloblastic anaemia, atypical hemolytic uremic syndrome, hyperhomocysteinaemia, microangiopathy, recurrent infections and autoimmune diseases
Created: 24 Aug 2021, 12:53 a.m. | Last Modified: 24 Aug 2021, 12:53 a.m.
Panel Version: 0.365

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinaemia MIM # 617780; Decreased Ig levels; poor antibody responses to conjugated polysaccharide antigens; low B/T/NK cells; Recurrent bacterial infection; megaloblastic anaemia; failure to thrive; neutropenia; seizures; intellectual disability; folate-responsive; Lymphopaenia

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Melbourne Genomics Health Alliance Immunology Flagship
  • Victorian Clinical Genetics Services
Phenotypes
  • Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinaemia MIM # 617780
  • Decreased Ig levels
  • poor antibody responses to conjugated polysaccharide antigens
  • low B/T/NK cells
  • Recurrent bacterial infection
  • megaloblastic anaemia
  • failure to thrive
  • neutropenia
  • seizures
  • intellectual disability
  • folate-responsive
  • Lymphopaenia
OMIM
172460
Clinvar variants
Variants in MTHFD1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

24 Aug 2021, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: mthfd1 has been classified as Green List (High Evidence).

24 Aug 2021, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: MTHFD1 were changed from to Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinaemia MIM # 617780; Decreased Ig levels; poor antibody responses to conjugated polysaccharide antigens; low B/T/NK cells; Recurrent bacterial infection; megaloblastic anaemia; failure to thrive; neutropenia; seizures; intellectual disability; folate-responsive; Lymphopaenia

24 Aug 2021, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: MTHFD1 were set to

24 Aug 2021, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: MTHFD1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

24 Aug 2021, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: MTHFD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal

17 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: MTHFD1 was added gene: MTHFD1 was added to Combined immunodeficiency_MelbourneGenomics_AustralianGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Immunology Flagship Mode of inheritance for gene: MTHFD1 was set to Unknown