Intellectual disability syndromic and non-syndromic
Gene: PIGA

PIGA (phosphatidylinositol glycan anchor biosynthesis class A)
EnsemblGeneIds (GRCh38): ENSG00000165195
EnsemblGeneIds (GRCh37): ENSG00000165195
OMIM: 311770, Gene2Phenotype
PIGA is in 15 panels

1 review

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

PMID 34875027: 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.
Created: 7 Apr 2022, 3:51 a.m. | Last Modified: 7 Apr 2022, 3:51 a.m.

Panel Version: 0.4662

At least 6 unrelated male patients have been reported.
Created: 27 Feb 2020, 1:46 a.m. | Last Modified: 27 Feb 2020, 1:46 a.m.

Panel Version: 0.2219

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM# 300868, MONDO:0010466; Neurodevelopmental disorder with epilepsy and haemochromatosis, MIM# 301072

Publications

Created: 27 Feb 2020, 1:46 a.m.
Last Modified: 27 Feb 2020, 1:46 a.m.
Panel version: 0.4662

Details

Mode of Inheritance

X-LINKED: hemizygous mutation in males, biallelic mutations in females

Sources

Expert Review Green
Genetic Health Queensland

Phenotypes

Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM# 300868, MONDO:0010466
Neurodevelopmental disorder with epilepsy and haemochromatosis, MIM# 301072

OMIM

311770

Clinvar variants

Variants in PIGA

Penetrance

None

Publications

Panels with this gene