Early onset or syndromic epilepsy

Gene: LNPK

Green List (high evidence)

Comment on list classification: There are three unrelated cases reported with epilepsy. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 23 Jul 2024, 4:54 p.m. | Last Modified: 23 Jul 2024, 4:54 p.m.

Panel Version: 5.30

PMID:35599435 reported a girl born to consanguineous healthy parent of Turkish descent with a novel LNPK variant (c.770delA/ p.D257fs*31). She presented with ataxia, psychomotor delay, cerebellar dysfunction and myoclonic seizures.

Created: 23 Jul 2024, 4:52 p.m. | Last Modified: 23 Jul 2024, 4:52 p.m.

Panel Version: 5.28

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum, OMIM:618090

Publications

• 35599435

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

I don't know

There are very few variants reported to be disease causing in LNPK, and all have come from the same source publication, PMID 30032983. The associated phenotype is severe and includes seizures/epilepsy.

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
Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum, 618090

Publications

• 30032983

Green List (high evidence)

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

Created: 24 Feb 2025, 5:59 p.m. | Last Modified: 24 Feb 2025, 5:59 p.m.

Panel Version: 7.39

Comment when marking as ready: Associated with phenotype in OMIM and not in Gen2Phen. At least 2 homozygous variants identified in 2 unrelated cases.

Created: 26 Sep 2018, 9:21 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

I don't know

3 individuals from two families; seizures are part of the phenotype.

Created: 16 Aug 2018, 11:37 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 30032983

I don't know

PMID 30032983 reports on 3 individuals (from 2 different consanguineous families) homozygous for loss-of-function variants in LNPK. The phenotype consisted of hypotonia, severe developmental delay, intellectual disability and seizures. MRI images demonstrated hypoplasia of the corpus callosum in all subjects and mild cerebellar hypoplasia and atrophy (in two of them). Functional studies were suggestive of absence of the full-length protein, more frequent aberrant endoplasmatic reticulum (ER) structures compared to controls and higher mass density within the ER.

This is the first report of the disorder.

Created: 14 Aug 2018, 7:54 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures; Hypoplasia of the corpus callosum; Abnormality of the cerebellum

Publications

• 30032983