Early onset or syndromic epilepsy
Gene: PIGW
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
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 variantCreated: 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
Comment when marking as ready: Sufficient cases to make greenCreated: 21 Nov 2018, 12:50 p.m.
Comment on list classification: 3 cases/families reported, all with seizuresCreated: 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.
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
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
Source Wessex and West Midlands GLH was added to PIGW.
Source NHS GMS was added to PIGW.
Zornitza Stark: Seizures are part of the pheno
Gene: pigw has been classified as Green List (High Evidence).
Phenotypes for gene: PIGW were changed from to Glycosylphosphatidylinositol biosynthesis defect 11, 616025; HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 5
Publications for gene: PIGW were set to 24367057; 27626616; 30078644
Publications for gene: PIGW were set to
Mode of inheritance for gene: PIGW was changed from to BIALLELIC, autosomal or pseudoautosomal
Gene: pigw has been classified as Green List (High Evidence).
Expert Review Amber was added to PIGW. Panel: Genetic Epilepsy Syndromes
PIGW was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
PIGW was created by Sarah Leigh