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Intellectual disability syndromic and non-syndromic

Gene: PIGA

Green List (high evidence)

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

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

History Filter Activity

7 Apr 2022, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: PIGA were changed from Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM#300868 to Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM# 300868, MONDO:0010466; Neurodevelopmental disorder with epilepsy and haemochromatosis, MIM# 301072

7 Apr 2022, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: PIGA were set to 24706016; 24259184; 29159939

27 Feb 2020, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

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

27 Feb 2020, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: PIGA were changed from to Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM#300868

27 Feb 2020, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: PIGA were set to

27 Feb 2020, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: PIGA was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females

22 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: PIGA was added gene: PIGA was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland Mode of inheritance for gene: PIGA was set to Unknown