Intellectual disability syndromic and non-syndromic
Gene: PIGW

PIGW (phosphatidylinositol glycan anchor biosynthesis class W)
EnsemblGeneIds (GRCh38): ENSG00000277161
EnsemblGeneIds (GRCh37): ENSG00000184886
OMIM: 610275, Gene2Phenotype
PIGW is in 4 panels

1 review

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

PMID: 24367057 - (2013) - A patient born to non-consanguineous parents developed intractable seizures with typical hypsarrhythmic pattern in electroencephalography, and was diagnosed as having West syndrome. Because the patient showed severe developmental delay with dysmorphic facial features and hyperphosphatasia, characteristics often seen in IGDs, the patient was tested for GPI deficiency. The patient had decreased surface expression of GPI-APs on blood granulocytes and was identified to be compound heterozygous for NM_178517:c.211A>C and c.499A>G mutations in PIGW.

PMID: 27626616 - (2016) Two second-degree cousins with unexplained patterns of seizures. Next-generation sequencing identified the homozygous c.460A>G; p.(R154G) PIGW mutation in both patients. Transfection of the mutated allele into Pigw-defective CHO cells indicated impaired enzymatic activity of the mutated PIGW product. The patients' phenotype is remarkably different from the phenotype of the only other described individual with PIGW mutations.

PMID: 30813920 - (2019) A Chinese boy with compound heterozygous PIGW mutations who suffers from severe pneumonia, mental retardation, and epilepsy. A 70-day-old boy presented with fever and cough over 20 days in duration at the time of admission. At the age of 6 months, unusual facial features were apparent, and seizures were clinically observed, accompanied by obvious cognitive delay. Next-generation sequencing identified novel PIGW c.178G > A and c.462A > T mutations

PMID: 32198969 - (2020) A new patient with a novel homozygous missense variant in PIGW, who presented with hypotonia, severe intellectual disability, early-onset epileptic seizures, brain abnormalities, nystagmus, hand stereotypies, recurrent respiratory infections, distinctive facial features, and hyperphosphatasia. Our report expands the phenotype of GPI biosynthesis defect 11 to include stereotypies and recurrent respiratory infections.

Summary - Multiple unrelated families reported with different recessive variants either homozygous or compound heterozygous. Functional studies showed impaired enzymatic activity
Created: 26 Apr 2022, 10:28 p.m. | Last Modified: 26 Apr 2022, 10:28 p.m.

Panel Version: 0.4698

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Glycosylphosphatidylinositol biosynthesis defect 11, MIM# 616025

Publications

Created: 26 Apr 2022, 10:28 p.m.
Last Modified: 26 Apr 2022, 10:28 p.m.
Panel version: 0.4698

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
Genetic Health Queensland

Phenotypes

Glycosylphosphatidylinositol biosynthesis defect 11, MIM# 616025

OMIM

610275

Clinvar variants

Variants in PIGW

Penetrance

None

Publications

Panels with this gene