Early onset or syndromic epilepsy

Gene: NEXMIF

Green List (high evidence)

Previously called KIAA2022. XLD MR98 - early onset seizures often seen. Van Maldergem et al, 2013 - 9 aff males from 4 unrelated families - seizures reported as a variable feature in aff males from 3 families identify 3 mutations2 result in premature term and the third a dup involving exon 1. Carrier females were unaff. Kuroda et al, 2015 - 2 unrelated Japanese boys - neither had seizures de novo hemizygous nonsense variants. Farach and Northup, 2016 - 17 year old girl - had refractory seizures since the age of 1 - de novo het nonsense mutation - patient had random X-inactivation pattern (73:27). De Lange et al, 2016 - 14 female patients with de novo het mutations - 12/14 had intractable epilepsy with myocolinc and/or absence seizures - de novo het truncating variants all predicted to result in LOF, X inactivation in 7 patients - 6 random whereas 1 100% skewing. Clinical variability thought to be due to X-inactivation and cellular interference. Webster et al, 2017 - 5 unrelated girls early onset intractable seizures - de novo trncating mutations - functional studies and studies of patient cells not performed.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Mental retardation, X-linked, 300912

Publications

• 23615299
• 27358180

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

Comment on mode of inheritance: Changed MOI from XLR to XLD to match the XLD recorded for 'Mental retardation, X-linked 98' in OMIM (MIM:300912) and Gene2Phenotype, which records X-linked dominant inheritance for 'Intellectual disability and epilepsy' in addition to hemizgyous inheritance for 'KIAA2022'. An XLD inheritance is supported by PMID:27358180 which reports 14 female patients who carry a heterozygous de novo KIAA2022 variant and share a phenotype characterised by intellectual disability and epilepsy.

Created: 11 Jul 2019, 7:44 a.m. | Last Modified: 11 Jul 2019, 7:44 a.m.

Panel Version: 1.149

Green List (high evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Publications

• 23615299

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

Green List (high evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Publications

• 23615299

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

Green List (high evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Publications

• 23615299

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

Green List (high evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Publications

• 23615299

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

added new-gene-name tag. Approved HGNC gene symbol is NEXMIF

Created: 1 Jun 2017, 2:24 p.m.

Comment on mode of inheritance: XLR (OMIM) and Hemizygous (G2P).

Created: 29 Jan 2016, 4:54 p.m.

Comment on phenotypes: Sourced from OMIM

Created: 20 Jan 2016, 1:33 p.m.

Gene added in expert review of the panel by Richard Scott (Genomics England), Manju Kurian (UCL-Institute of Child Health), Natalie Trump (NHS - Great Ormond Street Hospital), Amy McTague (UCL Institute of Child Health).

Created: 12 Nov 2015, 4:17 p.m.