Congenital Disorders of Glycosylation

Gene: PIGW

Amber List (moderate evidence)

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

2 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

I don't know

Downgraded to AMBER as rated LIMITED by ClinGen.
Created: 11 Mar 2025, 3:54 a.m. | Last Modified: 11 Mar 2025, 3:54 a.m.
Panel Version: 1.58

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Glycosylphosphatidylinositol biosynthesis defect 11, MIM# 616025

Dean Phelan (Victorian Clinical Genetics Services)

Green List (high evidence)

OMIM - Glycosylphosphatidylinositol biosynthesis defect 11, AR

Function - Glycosylphosphatidylinositol (GPI) is a complex glycolipid that anchors many proteins to the cell surface. PIGW acts in the third step of GPI biosynthesis and acylates the inositol ring of phosphatidylinositol

Clingen - no association with CGD

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: 15 Jul 2020, 12:30 a.m. | Last Modified: 15 Jul 2020, 12:33 a.m.
Panel Version: 0.57

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
intractable seizures; West syndrome; severe developmental delay; dysmorphic facial features; hyperphosphatasia; epilepsy; recurrent respiratory infections; hypotonia; stereotypies

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Victorian Clinical Genetics Services
Phenotypes
  • Glycosylphosphatidylinositol biosynthesis defect 11, MIM# 616025
OMIM
610275
Clinvar variants
Variants in PIGW
Penetrance
None
Publications
Panels with this gene

History Filter Activity

11 Mar 2025, Gel status: 2

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: PIGW were changed from Glycosylphosphatidylinositol biosynthesis defect 11, MIM# 616025; intractable seizures; West syndrome; severe developmental delay; dysmorphic facial features; hyperphosphatasia; epilepsy; recurrent respiratory infections; hypotonia; stereotypies to Glycosylphosphatidylinositol biosynthesis defect 11, MIM# 616025

11 Mar 2025, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: pigw has been classified as Amber List (Moderate Evidence).

15 Jul 2020, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

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

15 Jul 2020, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: PIGW were changed from to Glycosylphosphatidylinositol biosynthesis defect 11, MIM# 616025; intractable seizures; West syndrome; severe developmental delay; dysmorphic facial features; hyperphosphatasia; epilepsy; recurrent respiratory infections; hypotonia; stereotypies

15 Jul 2020, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: PIGW were set to

15 Jul 2020, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: PIGW 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: PIGW was added gene: PIGW was added to Congenital Disorders of Glycosylation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: PIGW was set to Unknown