Early onset or syndromic epilepsy

Gene: PIGC

Green List (high evidence)

Pons et al. 2020 (PMID: 32707268) report 2 sibs displaying severe psychomotor delay, seizures, organomegaly, cardiopulmonary anomalies, and similar facial dysmorphism. Sequencing revealed a homozygous variant in PIGC gene, c.12_13insTTGTGACTAACA leading to a premature stop codon p.(Gln4_Pro5insLeu*)

Created: 27 Apr 2021, 3:20 p.m. | Last Modified: 27 Apr 2021, 3:20 p.m.

Panel Version: 2.328

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Glycosylphosphatidylinositol biosynthesis defect 16, OMIM:617816

Publications

• 32707268

Green List (high evidence)

Two cases have been reported with Glycosylphosphatidylinositol biosynthesis defect-17 who had seizures, PMID: 29573052 (early-onset), 29603516 (febrile).

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 16, 617816

Publications

• 27694521

I don't know

As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Amber to Green.

Created: 13 Aug 2019, 4:24 p.m. | Last Modified: 15 Aug 2019, 8:07 a.m.

Panel Version: 1.223

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

Comment on list classification: Kept rating as Amber following external review by Zornitza Stark. Not yet associated with a disorder in Gene2Phenotype, and currently only 2 families from one paper identified in the literature (PMID:27694521) for PIGC.

Created: 1 Jul 2019, 3:12 p.m. | Last Modified: 1 Jul 2019, 3:12 p.m.

Panel Version: 1.95

PMID:27694521: Edvardson et al. 2017 studied 2 unrelated families (two siblings from consanguineous Moslem-Arab parents, and a son of unrelated Sephardic-Jewish parents) who suffered from global DD, ID and seizures. PIGC variants were found: homozygous p.L189W in one family, and compound het variant (L212P/R21X) in another.

Created: 1 Jul 2019, 3:06 p.m. | Last Modified: 1 Jul 2019, 3:10 p.m.

Panel Version: 1.89

I don't know

Seizures are part of the phenotype of this metabolic disorder; however, only two families reported.

Created: 18 Aug 2018, 10:38 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Glycosylphosphatidylinositol biosynthesis defect 16, MIM#617816

Publications

• 27694521

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