Early onset or syndromic epilepsy
Gene: LNPK
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
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
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.
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
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
Source Wessex and West Midlands GLH was added to LNPK.
Source NHS GMS was added to LNPK.
Konstantinos Varvagiannis: PMID 30032983 reports on 3 ind
Gene: lnpk has been classified as Amber List (Moderate Evidence).
Gene: lnpk has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: LNPK were changed from Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures; Hypoplasia of the corpus callosum; Abnormality of the cerebellum to Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum 618090
LNPK was added to Genetic Epilepsy Syndromes panel. Sources: Literature
LNPK was created by Konstantinos Varvagiannis