Early onset or syndromic epilepsy

Gene: KPTN

Green List (high evidence)

The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.

Created: 11 Oct 2023, noon | Last Modified: 11 Oct 2023, noon

Panel Version: 4.110

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

I don't know

There are relatively few variants reported in this gene, but there appears to be a founder effect in the Amish community, where some of the affected individuals had a seizure disorder PMID 24239382.

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
Mental retardation 41, 615637

Publications

• 24239382

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: Alison Callaway and John Taylor. Suggested gene rating: Amber.

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: Kept rating as Amber following evaluation of Green review by Zornitza. No further cases of KPTN variants associated with epilepsy/seizures are reported in the literature since PMID:24239382 (Baple et al., 2014: Founder effect in Amish community) and PMID:25847626 (Pajualu et al. 2015, 2 Estonian siblings with seizures in the brother). Although the association with ID is clearer, more epilepsy cases are required for a diagnostic-grade rating.

Created: 9 Jul 2019, 11:08 a.m. | Last Modified: 9 Jul 2019, 11:08 a.m.

Panel Version: 1.136

Green List (high evidence)

Two further publications (PMID 32358097; 32808430), more individuals reported with seizures, suggest upgrade to Green.

Created: 5 Oct 2020, 9:22 a.m. | Last Modified: 5 Oct 2020, 9:22 a.m.

Panel Version: 2.155

Please note several additional LP/P variants submitted by clinical laboratories in ClinVar, although of course it is difficult to know whether seizures were part of the phenotype.

Created: 16 Aug 2018, 2:19 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mental retardation, autosomal recessive 41, MIM#615637

Publications

• 32358097
• 32808430

Green List (high evidence)

Associated with relevant phenotype in OMIM and as strong Gen2Phen gene. At least five KPTN variants have been reported in four unrelated cases of OMIM: 615637, seizures were evident in three unrelated cases (PMID: 24239382;25847626;32358097;32808430).

Created: 14 Mar 2023, 4:37 p.m. | Last Modified: 14 Mar 2023, 4:37 p.m.

Panel Version: 3.111

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 14 Mar 2023, 4:32 p.m. | Last Modified: 14 Mar 2023, 4:32 p.m.

Panel Version: 3.111

Comment on list classification: Variants only reported in two families, seizures represent part of a variable phenotype in three individuals from the two families.

Created: 10 Apr 2018, 10:13 a.m.

Gene originally listed on the Intellectual disability panel V2.42.
Associated with relevant phenotypes in OMIM and as probable Gen2Phen gene. At least 3 variants reported in two families, seizures reported in 2 members of one family and in 1 member of the other family.

Created: 10 Apr 2018, 10:12 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mental retardation, autosomal recessive 41615637

Publications

• 24239382
• 25847626