Early onset or syndromic epilepsy

Gene: POMGNT1

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 macular dystrophy-dystroglycanopathy type 3A. Vervoot et al, 2004 - non-Finnish family - 2 sibs - 1 of which seemed more severe and developed epilepsy at 5 months - compound het variants. Biancheri et al, 2006 - Italian patient - had seizures - compound het for a splice and a nonsense variant. Mercuri et al, 2009 - 1 patient who had seizures along with other features - hom truncating nonsense variant.

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
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) type A, 3 253280; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation)type B, 3 613151; Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 3 613157 ; Retinitis pigmentosa 76 617123

Publications

• 15466003

Comment on list classification: > 3 cases with variants in this gene and seizures so rating green.

Created: 5 Dec 2018, 11:54 a.m.

Associated with Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 along with other types of Muscular dystrophy-dystroglycanopathy in OMIM and Gene2Phenotype.

Numerous variants and cases reported in OMIM.

PMID: 24282183 (Raducu et al 2014) report a case of a child with Muscle-eye-brain disease, 2 heterozygous mutations in the POMGNT1 gene and seizure at age 7.

PMID: 15236414 (Vervoort et al 2004) report a family with 2 siblings with Muscle‐eye‐brain disease. Both are compound hetrozygotes with two missense changes in POMGNT1. 1 child is reported to have epileptic seizures from 5 months.

PMID:17878207 (Godfrey et al 2007) report 7 patients with compound heterozygous or homozygous variants in POMGNT1 (subjects 18-24). 3 are reported to have seizures.

Created: 5 Dec 2018, 11:53 a.m.

Green List (high evidence)

Seizures are part of the phenotype of dystroglycanopathies.

Created: 19 Aug 2018, 11:21 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3, MIM#253280

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