Early onset or syndromic epilepsy

Gene: GPAA1

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: 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

Green List (high evidence)

AR glycosylphosphatidylinositol biosynthesis defect 15. Characterised by delayed psychomotor development, variable intellectual disability, hypotonia, early onset seizures in most patients and cerebellar atrophy. Nguyen et al, 2017 - 10 patients from 5 unrelated families of GPIBD15. 7 patients from 4 families had onset of generalised seizures within the first 2 years of life. Hom or compound het mutations identified and segregated with disease in all families - 6 missense, 2 s, 1 splicing. Cells derived from several of the patients showed variably decreased amounts of GPI-anchored proteins on the cell surface - defects partially rescued by expression of wildtype GPAA1. Some transfection studies also done. Of note no compound het of fs and splicing were reported.

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 15,617810

Publications

• 29100095

Green List (high evidence)

Associated with phenotype in OMIM. At least 7 variants reported in 10 patients from 5 unrelated families with Glycosylphosphatidylinositol biosynthesis defect 15 (617810). The patients ranged in age from 3.8 to 30 years. All had mild to moderate intellectual disability, together with other features of developmental delay and early-onset seizures in the majority of cases.

Created: 15 Mar 2018, 1:36 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Glycosylphosphatidylinositol biosynthesis defect 15, 617810

Publications

• 29100095
• 24896178