Early onset or syndromic epilepsy
Gene: DPAGT1
AR congenital myasthenic syndrome with tubular aggregates and AR congenital disorder of glycosylation type Ij. Wurde et al, 2012 - 2 sibs - consang Turkish parents - intractable seizures - death in first year of life - hom DPAGT1 missense variant - RT-PCR analysis showed the mutation increased the amount of normal aberrant splicing in controls , resulting in the skipping of exons 2 & 3 and lead to a truncated protein, in vitro studies done. Iqbal et al, 2013 - Pakistani brother and sister - both develped seizures in childhood - compound het missense variants. Ng et al, 2019 - 14 disease causing mutations in 28 patients from 10 families have prev been reported- in this paper they report another 11 patients from 8 families and add 10 new mutations - approx 50% have epilepsy.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
Congenital disorder of glycosylation type Ij, 608093; Myasthenic syndrome congenital, 13 with tubular aggregates, 614750
Publications
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
Comment on list classification: Updated rating from Amber to Green: Green review. Confirmed DD-G2P gene for Congenital disorder of glycosylation (CDG), which can present with seizures. Sufficient cases of seizures from the literature (3 cases from PMIDs:22304930, 23249953, 12872255) for inclusion on panel.Created: 24 Nov 2018, 9:33 p.m.
In a patient with central disorder of glycosylation type Ij, Wu et al. (2003, PMID:12872255) identified reduced DPAGT1 enzymatic activity. In the paternal allele, a variant Y170C was identified. Although no variant was identified in the maternal allele, it produced only 12% of the normal amount of mRNA. She had severe hypotonia and medically intractable seizures amongst her phenotypes.Created: 24 Nov 2018, 9:22 p.m.
In a Pakistani brother and sister born of unrelated patients with a mild form of CDG Ij, Iqbal et al. (2013, PMID:23249953) identified compound heterozygous mutations in the DPAGT1 gene (I29F and L168P). The patients had normal psychomotor development until ages 2 and 5 years, respectively, when they both developed seizures, hypotonia, and aggressive behavior. Seizures and additional phenotypes continued into adulthood.Created: 24 Nov 2018, 9:21 p.m.
In 2 sibs, born of consanguineous Turkish parents, with severe CDG Ij, Wurde et al. 2012 (PMID:22304930) identified a homozygous mutation in the DPAGT1 gene (p.A114G). The patients had a severe form which included intractable seizures, and died within the first year of life.Created: 24 Nov 2018, 9:19 p.m.
Seizures are a feature of this multi system metabolic disorder.Created: 12 Aug 2018, 6:52 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Congenital disorder of glycosylation, type Ij, MIM#608093
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to DPAGT1.
Source NHS GMS was added to DPAGT1.
Zornitza Stark: Seizures are a feature of this
Gene: dpagt1 has been classified as Green List (High Evidence).
Gene: dpagt1 has been classified as Green List (High Evidence).
Mode of inheritance for gene: DPAGT1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DPAGT1 were changed from to Congenital disorder of glycosylation, type Ij, 608093
Expert Review Amber was added to DPAGT1. Panel: Genetic Epilepsy Syndromes
DPAGT1 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
DPAGT1 was created by Sarah Leigh