Early onset or syndromic epilepsy

Gene: PIGM

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 2 May 2024, 1:13 p.m. | Last Modified: 6 May 2024, 9:21 p.m.

Panel Version: 5.6

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

PMID: 31445883 - two new families reported, with same promoter region variant

Created: 16 Nov 2023, 2:24 p.m. | Last Modified: 16 Nov 2023, 2:24 p.m.

Panel Version: 4.74

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Glycosylphosphatidylinositol deficiency 610293

Publications

• 31445883

Green List (high evidence)

A single PIGM variant (NM_145167.2(PIGM):c.-270C>G)(rs587776528) has been associated with Glycosylphosphatidylinositol deficiency, (OMIM:610293) and as limited Gen2Phen gene for the same condition.
To date, this variant has only been reported in people of Arab or Turkish descent. Microsatellite- and SNP-based haplotypes encompassing PIGM reported in PMID:19168132, suggested that a founder effect in the two families (one Arab and one Turkish) was unlikely. However, subsequent occurrences of the variant in two additional unrelated Arab families (PMID: 31445883) might suggest that this variant is confined within the Middle Eastern populations.
Functional studies have shown that this variant reduces transcription of PIGM and blocks mannosylation of glycosylphosphatidylinositol anchor (PMID: 16767100).
Absence seizures were apparent in 5/7 individuals from 5/6 families with OMIM:610293 biallelic for rs587776528 (table 1, PMID: 31445883).

Created: 21 Nov 2023, 2:34 p.m. | Last Modified: 21 Nov 2023, 2:42 p.m.

Panel Version: 4.129

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 21 Nov 2023, 2:07 p.m. | Last Modified: 21 Nov 2023, 2:07 p.m.

Panel Version: 4.77

Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 1 variant was reported in 2 unrelated families (PMID 16767100), together with supportive functional studies (PMID 17442906 & 25293775).

Created: 19 Aug 2019, 3:45 p.m. | Last Modified: 19 Aug 2019, 3:45 p.m.

Panel Version: 1.232

Comment on phenotypes: Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation;Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency

Created: 19 Aug 2019, 3:23 p.m. | Last Modified: 19 Aug 2019, 3:23 p.m.

Panel Version: 1.228

Added tags to indicate a promoter variant has been reported.

Created: 1 Mar 2017, 11:54 a.m.

Red List (low evidence)

Associated with phenotype in OMIM, not in G2P. At least 1 promoter variant reported in 3 cases from 2 unrelated consanguineous families. PIGM is subject to cell-type specific transcriptional regulation

Created: 23 Feb 2017, 5:15 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Glycosylphosphatidylinositol deficiency 610293

Publications

• 16767100
• 25293775