Early onset or syndromic epilepsy

Gene: PIGN

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 multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1). Mayden et al, 2011 - 7 patients from a large consang Arab Israeli kindred - 6 had seizures - hom missense variant. Ohba et al, 2014 - 2 Japanese sibs - both had seizures - compound het mutations - expression studies support pathogenicity. Khayet et al, 2016 - proband to consang Arab-Israeli parents - seizures. FH was significant with 2 spontaneous abortions and a brother who died at 12 days of a congenital diaphragmatic hernia - hom missense variant exprtession studies support pathogenicity. Fleming et al, 2016 - 4 patients from 3 unrelated families -all had seizures. The 2 sibs were compund het for a nonsense and a missense variant, another patient with a milder phenotype hwas compund het for two missense variants, and the last patient who was severely affected was a compund het for a fs and an intragenic deletion.

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
Multiple congenital anomalies-hypotonia-seizures syndrome, 614080

Publications

• 24253414
• 21493957

Green List (high evidence)

Gene originally listed on the Intellectual disability panel V2.42.
Associated with relevant phenotypes in OMIM and as probable Gen2Phen gene. At least 11 variants reported.

Created: 10 Apr 2018, 12:45 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Multiple congenital anomalies-hypotonia-seizures syndrome 1 614080

Publications

• 26419326
• 27038415
• 26394714