Early onset or syndromic epilepsy

Gene: KIAA1109

As a result of watchlist tag audit the watchlist tag was removed from KIAA1109- this is now a green gene with sufficient evidence/review

Created: 13 Jan 2020, 1:54 p.m. | Last Modified: 13 Jan 2020, 1:54 p.m.

Panel Version: 2.0

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Alkuraya-Kucinskas syndrome, 617822

Publications

• 29290337

I don't know

As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green- although epilepsy may be secondary to the cerebral malformations presentation, include KIAA1109 so that cases recruited through different routes are not missed. Promoted from Amber to Green.

Created: 13 Aug 2019, 4:22 p.m. | Last Modified: 15 Aug 2019, 8:06 a.m.

Panel Version: 1.223

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: Green.

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: Re-assessed gene:disease evidence based on 2019 paper (PMID:30906834). Kept rating as Amber awaiting further information: seizures present in 2 Lithuanian siblings (PMID:29290337) plus two African-American siblings (PMID:30906834). Plus Drosophila model (PMID:19640479). There is limited patient information because severe LOF alleles are incompatible with life.

Created: 1 Jul 2019, 2:46 p.m. | Last Modified: 1 Jul 2019, 2:47 p.m.

Panel Version: 1.89

PMID:30906834: Kane et al. 2019 report two brothers from non-consanguineous African-American parents with compound het KIAA1109 variants presenting with neurological malformations, severe DD and hypotonia. The older brother (patient A) developed focal seizures age 4 months. The younger brother (patient B) developed seizures at 61 days.

Created: 1 Jul 2019, 1:45 p.m. | Last Modified: 1 Jul 2019, 1:45 p.m.

Panel Version: 1.86

Added new-gene-name tag, new approved HGNC gene symbol for KIAA1109 is BLTP1.

Created: 30 Jun 2022, 3:32 p.m. | Last Modified: 30 Jun 2022, 4:09 p.m.

Panel Version: 2.542

Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene (although not for seizures in Gen2Phen). At least 2 variants reported in Lithuanian siblings with Alkuraya-Kucinskas syndrome in which seizures were a phenotypic feature (PMID 29290337). Rare drosophila idividuals that are homozygous for a "tweek" variant (ortholog KIAA1109) survive to adulthood and are unable to walk or stand upright for long periods, plus they exhibit seizures, suggestive of severe neurological defects and similar to the reported phenotype of the Lithuanian siblings mentioned (PMID 19640479).

Created: 6 Dec 2018, 3:26 p.m.

I don't know

Bi-allelic variants cause a severe neurological phenotype characterised by early lethality. Small number of survivors described to date, some of whom had seizures.

Created: 16 Aug 2018, 1:56 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Alkuraya-Kucinskas syndrome, MIM#617822

Publications

• 29290337

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