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Genetic epilepsy syndromes

Gene: PIGW

Green List (high evidence)

PIGW (phosphatidylinositol glycan anchor biosynthesis class W)
EnsemblGeneIds (GRCh38): ENSG00000277161
EnsemblGeneIds (GRCh37): ENSG00000184886
OMIM: 610275, Gene2Phenotype
PIGW is in 6 panels

5 reviews

Rebecca Foulger (Genomics England curator)

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.
Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

AR glycosylphosphatidylinositol biosynthesis defect 11 - neonatal hypotonia, lack of psychomotor development and variable seizures. Chiyonobu et al, 2014 - Japanese male infnt born of unrelated parents tonic clonic seizures - compound het missense mutations, in vitro expression studies done. Hogrebe et al, 2016 - 2nd degree cousins - both developed seizures - hom missense variants, transfection studies done. Peycheva et al, 2018 - dup incl this gene and others - proband had refractory seizures as did her sister who also had epilepsy - although they say that a few genes could be contributing to the phenotype (LHX1, PIGW and ACACA). Foskett et al, 2018 - patient with myoclonic seizures, hom for PIGW missense variant
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Glycosylphosphatidylinositol biosynthesis defect, 616025

Publications

Eleanor Williams (Genomics England Curator)

Comment when marking as ready: Sufficient cases to make green
Created: 21 Nov 2018, 12:50 p.m.
Comment on list classification: 3 cases/families reported, all with seizures
Created: 21 Nov 2018, 12:44 p.m.
Associated with Glycosylphosphatidylinositol biosynthesis defect 11 in OMIM and in HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 5 in Gene2Phenotype (possible).

2 cases of mutations in PIGW in patients with glycosylphosphatidylinositol biosynthesis defect-11 reported in Chiyonobu et al. (2014)(PMID: 24367057) - compound heterozygous missense mutations, and Hogrebe et al. (2016) (PMID: 27626616) - homozygous missense. In both families seizures were observed.

A third case is reported by Foskett et al 2018 (PMID: 30078644) -an infant was homozygous for variants in PIGW (c.199C>G; p.Pro67Ala) with an associated phenotype of infantile spasms, myoclonic seizures, cortical visual impairment, developmental delay, and minor dysmorphic features. Significantly decreased expression of important glycosylphosphatidylinositols was observed.
Created: 21 Nov 2018, 12:41 p.m.

Konstantinos Varvagiannis (Other)

Green List (high evidence)

PMID: 30078644 is a further report on the disorder. One individual homozygous for a missense variant is described. The phenotype included infantile spasms, profound developmental delay as well as additional features. The patient was homozygous for a missense variant [p.(Pro67Ala)], predicted to be pathogenic by 2 (out of 3) in silico prediction algorithms. Serum alkaline phosphatase (ALP) was elevated on two occasions. Flow cytometry was performed and demonstrated significantly decreased expression of GPIs, further supporting pathogenicity. The specific patient was tested using a diagnostic panel for epilepsy.

PIGW is included in gene panels for intellectual disability and/or epilepsy offered by different diagnostic labs.

As a result, this gene can be considered for possible upgrade to green.
Created: 16 Oct 2018, 10:04 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Variants in this GENE are reported as part of current diagnostic practice

Zornitza Stark (Australian Genomics)

I don't know

Seizures are part of the phenotype in this metabolic disorder; however, only two families described in the literature.
Created: 19 Aug 2018, 11:05 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Glycosylphosphatidylinositol biosynthesis defect 11, MIM#616025

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Wessex and West Midlands GLH
  • NHS GMS
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • Glycosylphosphatidylinositol biosynthesis defect 11, 616025
  • HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 5
OMIM
610275
Clinvar variants
Variants in PIGW
Penetrance
None
Publications
Panels with this gene

History Filter Activity

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to PIGW.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to PIGW.

11 Dec 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Zornitza Stark: Seizures are part of the pheno

21 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

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

21 Nov 2018, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: PIGW were changed from to Glycosylphosphatidylinositol biosynthesis defect 11, 616025; HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 5

21 Nov 2018, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: PIGW were set to 24367057; 27626616; 30078644

21 Nov 2018, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: PIGW were set to

21 Nov 2018, Gel status: 3

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: PIGW was changed from to BIALLELIC, autosomal or pseudoautosomal

21 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

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

25 Jun 2018, Gel status: 2

Added New Source

Sarah Leigh (Genomics England Curator)

Expert Review Amber was added to PIGW. Panel: Genetic Epilepsy Syndromes

25 Jun 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

PIGW was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services

25 Jun 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

PIGW was created by Sarah Leigh