Early onset or syndromic epilepsy
Gene: KPTN
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
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
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
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
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
Tag Q1_23_promote_green was removed from gene: KPTN.
Source Expert Review Green was added to KPTN. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag watchlist was removed from gene: KPTN. Tag Q1_23_promote_green tag was added to gene: KPTN.
Gene: kptn has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: KPTN were changed from Mental retardation, autosomal recessive 4,1615637; seizures to Intellectual developmental disorder, autosomal recessive 41, OMIM:615637; macrocephaly-developmental delay syndrome, MONDO:0014289
Publications for gene: KPTN were set to 24239382; 25847626
Source Wessex and West Midlands GLH was added to KPTN.
Source NHS GMS was added to KPTN.
Phenotypes for gene: KPTN were changed from Mental retardation, autosomal recessive 41615637 to Mental retardation, autosomal recessive 4,1615637; seizures
Gene: kptn has been classified as Amber List (Moderate Evidence).
Sarah Leigh: Gene originally listed on the
Gene: kptn has been classified as Amber List (Moderate Evidence).
This gene has been classified as Amber List (Moderate Evidence).
KPTN was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review
KPTN was created by Sarah Leigh