Early onset or syndromic epilepsy
Gene: PHGDH
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 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
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.
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
Source Wessex and West Midlands GLH was added to PHGDH.
Source NHS GMS was added to PHGDH.
Zornitza Stark: Seizures are part of the pheno
Gene: phgdh has been classified as Green List (High Evidence).
Phenotypes for gene: PHGDH were changed from to Phosphoglycerate dehydrogenase deficiency 601815
Publications for gene: PHGDH were set to
Mode of inheritance for gene: PHGDH was changed from to BIALLELIC, autosomal or pseudoautosomal
Gene: phgdh has been classified as Green List (High Evidence).
Expert Review Amber was added to PHGDH. Panel: Genetic Epilepsy Syndromes
PHGDH was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
PHGDH was created by Sarah Leigh