Metal Metabolism Disorders
Gene: PIGAEnsemblGeneIds (GRCh38): ENSG00000165195
EnsemblGeneIds (GRCh37): ENSG00000165195
OMIM: 311770, Gene2Phenotype
PIGA is in 15 panels
2 reviews
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Neurodevelopmental disorder with epilepsy and hemochromatosis, MIM# 301072
Alison Yeung (Victorian Clinical Genetics Services)
Heterozygous variants in PIGA causing a neurodevelopment disorder and a juvenile form of hereditary hemochromatosis reported in > three unrelated patients. All patients had increased serum iron, ferritin and transferrin saturation levels, high ALP and low hepcidin. All patients had generalised seizures and intellectual disability. A subpopulation of patient blood cells showed a slight reduction of GPI-anchored proteins, suggesting that the mutations were hypomorphic and retained some residual activity. CRISPR/Cas12a-mediated knockdown of PIGA in Hep3B liver cells eliminated the cell surface expression of GPI-anchored proteins CD59 and hemojuvelin (HJV; 608374), as well as caused decreased expression of hepcidin (606464) compared to controls. These hypomorphic alleles could explain the milder neurologic phenotype, which allowed for sufficiently long survival for the iron overload phenotype to manifest.
Sources: LiteratureCreated: 7 Apr 2022, 1:27 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Neurodevelopmental disorder with epilepsy and hemochromatosis, MIM# 301072
Publications
Details
- Mode of Inheritance
- X-LINKED: hemizygous mutation in males, biallelic mutations in females
- Sources
-
- Expert Review Green
- Literature
- Phenotypes
-
- Neurodevelopmental disorder with epilepsy and hemochromatosis, MIM# 301072
- OMIM
- 311770
- Clinvar variants
- Variants in PIGA
- Penetrance
- None
- Publications
- Panels with this gene
-
- Mackenzie's Mission_Reproductive Carrier Screening
- Clefting disorders
- Prepair 1000+
- BabyScreen+ newborn screening
- Hydrops fetalis
- Metal Metabolism Disorders
- Intellectual disability syndromic and non-syndromic
- Bleeding and Platelet Disorders
- Genetic Epilepsy
- Congenital Disorders of Glycosylation
- Fetal anomalies
- Additional findings_Paediatric
- Mendeliome
- Callosome
- Cerebral Palsy
History Filter Activity
Set mode of inheritance
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Mode of inheritance for gene: PIGA was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Entity classified by Genomics England curator
Alison Yeung (Victorian Clinical Genetics Services)Gene: piga has been classified as Green List (High Evidence).
Entity classified by Genomics England curator
Alison Yeung (Victorian Clinical Genetics Services)Gene: piga has been classified as Green List (High Evidence).
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes
Alison Yeung (Victorian Clinical Genetics Services)gene: PIGA was added gene: PIGA was added to Iron metabolism disorders. Sources: Literature Mode of inheritance for gene: PIGA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PIGA were set to 34875027 Phenotypes for gene: PIGA were set to Neurodevelopmental disorder with epilepsy and hemochromatosis, MIM# 301072 Review for gene: PIGA was set to GREEN