Early onset or syndromic epilepsy

Gene: PHGDH

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 phosphoglycerate dehydrogenase deficiency - characterised by congenital microcephaly, psychomotor retardation and seizures. Jaeken et al, 1996 - 2 Turkish brothers - consang - both had epilepsy. Klomp et al, 2000 - variants detected in 6 patients from 4 families and in vitro studies done (Patients prev reported by Koning et al, 1998, Jaeken et al, 1996 & Pineda et al, 2000). Tabatabie et al, 2009 - 3 Dutch patients including a borther and sister ad 2 unrelated Turkish parents who all presented with this disease incl seizures - compound het or hom for 5 diff mutations, funcxtional studies done.

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
Neu-Laxova syndrome, 256520; Phosphoglycerate dehydrogenase deficiency, 601815

Publications

• 11751922

Comment when marking as ready: Sufficient cases reported with seizures.

Created: 21 Nov 2018, 12:23 a.m.

Comment on list classification: More than 3 variants associated with the disorder. Patients from 7 families present with seizures.

Created: 20 Nov 2018, 11:43 p.m.

PHGDH is associated with Phosphoglycerate dehydrogenase deficiency in OMIM and Gene2Phenotype. Seizures are part of the phenotype of this disorder.

More than 3 variants are associated with Phosphoglycerate dehydrogenase deficiency in OMIM.

Klomp et al. (2000)(PMID: 11055895) report 5 patients from 3 different families were homozygous for a single nucleotide substitution predicted to change valine at position 490 to methionine. Patients from each family are reported to have seizures.

Tabatabaie et al. (2009) (PMID: 19235232) identified 1 frameshift and 4 missense mutations in the PHGDH gene in 5 patients with phosphoglycerate dehydrogenase deficiency. All presented with seizures.

Created: 20 Nov 2018, 11:42 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this metabolic disorder.

Created: 18 Aug 2018, 10:35 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Phosphoglycerate dehydrogenase deficiency, MIM#601815

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