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Genetic epilepsy syndromes

Gene: PIGQ

Green List (high evidence)

PIGQ (phosphatidylinositol glycan anchor biosynthesis class Q)
EnsemblGeneIds (GRCh38): ENSG00000007541
EnsemblGeneIds (GRCh37): ENSG00000007541
OMIM: 605754, Gene2Phenotype
PIGQ is in 4 panels

10 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: Alison Callaway and John Taylor. 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)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Glycosylphosphatidylinositol biosynthesis defect

Publications

Eleanor Williams (Genomics England Curator)

Comment on list classification: 3 cases plus some functional data.
Created: 19 Jun 2019, 9:30 a.m.
Not associated with a phenotype in OMIM although one variant from Martin et al 2014 is noted.
In Gene2Phenotype there is a possible association with SEVERE EARLY-ONSET EPILEPSY (ballelic)

PMID: 24463883 - Martin et al 2014 - 1 case. A child of West African origin, had severe early-onset epilepsy with a burst-suppression EEG, consistent with Ohtahara Syndrome. A homozygous A-to-G transition in intron 2 of the PIGQ gene (c.690-2A-G), resulting in the skipping of exon 3 and an in-frame deletion of 44 amino acids. The mutation was confirmed by Sanger sequencing and segregated with the disorder in the family. Some functional data: transfection of the mutation into PIGQ-deficient CHO cells did not restore GPI-anchored protein expression as efficiently as wildtype, and expression of the mutant protein was decreased compared to wildtype, consistent with a loss-of-function effect. The patient had onset of refractory seizures at age 4 weeks. 

PMID: 25558065 - Alazami et al 2015 - 1 case with consanguineous parents listed in Table S1 with a variant in PIGQ (NM_004204.3:c.619C>T:p.R207*) and Intractable seizure, developmental delay, and optic atrophy.

PMID: 31148362 - Starr et al 2019 - describe a patient with a multisystem disorder including epilepsy. He was compound heterozygous for two variants in PIGQ; a maternal frameshift mutation c.968_969delTG (p.L323Pfs*119) resulting in premature protein truncation and a paternal origin in‐frame deletion c.1199_1201delACT (p.Y400del).  The authors state that the three patients support evidence for a new syndrome—PIGQ‐related GPI‐AP biosynthesis deficiency syndrome.

The recent Deb Pal review is referencing the Martin et al paper.

Summary: There are now 3 cases of patients with plausible disease causing variants in this gene and disorders that have epilepsy as part of the phenotype.
Created: 19 Jun 2019, 9:29 a.m.

Deb Pal (King's College London)

Red List (low evidence)

Amplexa CHE-114 epilepsy panel
Created: 21 Feb 2019, 2:29 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
epilepsy; Ohtahara syndrome

Publications

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

Louise Daugherty (Genomics England Curator)

I don't know

Comment on list classification: changed from Red to Amber Changed from Amber to Green. Appropriate phenotypes, sufficient cases, and external review comment all support gene-disease association.
Created: 11 Dec 2018, 2:34 p.m.
Comment on phenotypes: added phenotype from expert review
Created: 11 Dec 2018, 2:28 p.m.
Comment on publications: added publication suggested by external reviewer
Created: 11 Dec 2018, 2:23 p.m.
Transferred over Review by Alistair Pagnamenta (University of Oxford) 5 Dec 2018, 12:39 p.m.
from Panel version: 1.147 Panel name: Epileptic encephalopathy.

Alazami et al identified a patient with "Intractable seizure, developmental delay and optic atrophy" and homozygous c.619C>T; p.Arg207Ter variant in this gene. See www.ncbi.nlm.nih.gov/clinvar/variation/183339/ and supplemental data for PMID: 25558065. I'm not sure if this is sufficient to upgrade to amber but nevertheless worth highlighting as there is phenotypic overlap with patient described in Martin et al and none of the other reviews mention this study.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intractable seizures; developmental delay; optic atrophy

Publications
PMID: 25558065
Created: 11 Dec 2018, 2:22 p.m.

Amy McTague (UCL Institute of Child Health)

Red List (low evidence)

Publications

  • Martin et al (2014) Hum Mol Genet 23(12).3200-3211

Natalie Trump (NHS - Great Ormond Street Hospital)

Red List (low evidence)

Publications

  • Martin et al (2014) Hum Mol Genet 23(12).3200-3211

Manju Kurian (UCL-Institute of Child Health)

Red List (low evidence)

Publications

  • Martin et al (2014) Hum Mol Genet 23(12).3200-3211

Richard Scott (North Thames GMC/UCL)

Red List (low evidence)

Publications

  • Martin et al (2014) Hum Mol Genet 23(12).3200-3211

Ellen McDonagh (Genomics England Curator)

Gene added in expert review of the panel by Richard Scott (Genomics England), Manju Kurian (UCL-Institute of Child Health), Natalie Trump (NHS - Great Ormond Street Hospital), Amy McTague (UCL Institute of Child Health).
Created: 12 Nov 2015, 4:18 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Wessex and West Midlands GLH
  • NHS GMS
  • Expert Review Green
  • Expert Review
Phenotypes
  • Epileptic encephalopathy, early infantile, 77, 618548
  • Intractable seizures
  • developmental delay
  • optic atrophy
  • epilepsy
  • Ohtahara syndrome
OMIM
605754
Clinvar variants
Variants in PIGQ
Penetrance
None
Publications
Panels with this gene

History Filter Activity

3 Oct 2019, Gel status: 3

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: PIGQ were changed from Intractable seizures; developmental delay; optic atrophy; epilepsy; Ohtahara syndrome to Epileptic encephalopathy, early infantile, 77, 618548; Intractable seizures; developmental delay; optic atrophy; epilepsy; Ohtahara syndrome

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to PIGQ.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to PIGQ.

19 Jun 2019, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: PIGQ were changed from Intractable seizures; developmental delay; optic atrophy to Intractable seizures; developmental delay; optic atrophy; epilepsy; Ohtahara syndrome

19 Jun 2019, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: PIGQ were set to 24463883; 25558065

19 Jun 2019, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

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

11 Dec 2018, Gel status: 2

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Ellen McDonagh: Gene added in expert review of

11 Dec 2018, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

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

11 Dec 2018, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

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

11 Dec 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: PIGQ were set to Martin et al (2014) Hum Mol Genet 23(12).3200-3211; 25558065

11 Dec 2018, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: PIGQ were changed from BIALLELIC, autosomal or pseudoautosomal to Intractable seizures; developmental delay; optic atrophy

11 Dec 2018, Gel status: 1

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

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

11 Dec 2018, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: PIGQ were changed from to BIALLELIC, autosomal or pseudoautosomal

11 Dec 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: PIGQ were set to Martin et al (2014) Hum Mol Genet 23(12).3200-3211

4 Apr 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

PIGQ was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Red,Expert Review

4 Apr 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

PIGQ was created by Sarah Leigh