Early onset or syndromic epilepsy

Gene: OCLN

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 pseudo-TORCH syndrome 1 (PTORCH1) - Neurological disorder with characteristic clinical and neuroradiologic features that mimic TORCH infection in the absence of evidence of infection. Aff individuals have congenital microcephayl, intracranial calcifications, severe develpmental delay, simplified gyration and polymicrogyria. Refractory seizures are a feature. O'Driscoll et al, 2010 - In 9 individuals from 6 families hom/compound het mutations in the OCLN gene. Microarray analysis identified hom deletions of copy no probes between exons 3 and 4 in aff individuals from 2 unrelated consang families. 5/6 families had deletions or variants affecting the Marvel domain - suggesting that the OCLN mutations result in a protein product that fails to locate to tight junctions in the cell membrane. Jenkinson et al, 2018 - 4 additional cases with novel OCLN mutations. Abdel-Hamid et al, 2017 - 13 new patients from 10 unrelated Egyptian families - identified 5 novel variants - all had seizures

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
Pseudo-TORCH syndrome, 251290

Publications

• 28386946

Comment when marking as ready: Sufficient cases with variants in OCLN and seizures reported.

Created: 14 Nov 2018, 2:51 p.m.

Comment on list classification: More than 3 cases/variants reported in OCLN in patients with Pseudo-TORCH syndrome 1. At least 3 families with reports of seizures in newborns.

Created: 14 Nov 2018, 2:49 p.m.

Associated with Pseudo-TORCH syndrome 1 (a.k.a Band-like calcification with simplified gyration and
polymicrogyria (BLC-PMG)) in OMIM but not Gene2Phenotype.

OMIM reports that in 9 individuals from 6 families with pseudo-TORCH syndrome-1, O'Driscoll et al. (2010)(PMID: 20727516) identified homozygous or compound heterozygous mutations in the OCLN gene. 4 variants reported in OMIM. At least 4 of the patients from 3 families presented with seizures within 6 weeks after birth (the new cases reported in O'Driscoll).

Created: 14 Nov 2018, 2:45 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this multi-system developmental disorder.

Created: 18 Aug 2018, 8:36 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pseudo-TORCH syndrome 1, MIM#251290

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