Early onset or syndromic epilepsy
Gene: PIGM
PMID: 31445883 - two new families reported, with same promoter region variantCreated: 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
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 deficiencyCreated: 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.
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 regulationCreated: 23 Feb 2017, 5:15 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Glycosylphosphatidylinositol deficiency 610293
Publications
Tag Q4_23_NHS_review was removed from gene: PIGM.
gene: PIGM was added gene: PIGM was added to Early onset or syndromic epilepsy. Sources: NHS GMS,Expert Review Amber,London North GLH promoter, non-coding-known-pathogenic, Q4_23_promote_green, Q4_23_NHS_review tags were added to gene: PIGM. Mode of inheritance for gene: PIGM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIGM were set to 27604308; 16767100; 25293775; 17442906; 31445883 Phenotypes for gene: PIGM were set to Glycosylphosphatidylinositol deficiency, OMIM:610293