Early onset or syndromic epilepsy
Gene: CNNM2
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: John Taylor and Helen Lord. 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
AD & AR hypomagnesia, seizures and mental retardation - onset of seizures assoc with low serum magnesium in first year of life. Arjona et al, 2014 - 3 unrelated German patients - onset of seizures assoc with low serum magnesium in first year of life. 2 diff de novo het missense mutations. In addition 2 sibs from a consang Serbian family who presented with seizutres in the neonatal period were hom for a missense variant. In vitro studies were consistent with LOF mutationCreated: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Hypomagnesemia renal, 613882; Hypomagnesemia, seizures, and mental retardation 616418
Publications
Comment on phenotypes: Monoallelic variants are also associated with Hypomagnesemia 6, renal 613882, but this condition does not include seizuresCreated: 9 Apr 2018, 4:52 p.m.
Gene originally listed on the Intellectual disability panel V2.42.
Associated with phenotype in OMIM and not in Gen2Phen. At least 3 variants identified in 3 unrelated cases (one case was homozygous). Supporting functional studies were provided for each variant (PMID 24699222).Created: 9 Apr 2018, 4:51 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Hypomagnesemia, seizures, and mental retardation 616418
Publications
Phenotypes for gene: CNNM2 were changed from Hypomagnesemia, seizures, and mental retardation 616418 to Hypomagnesemia, seizures, and mental retardation, OMIM:616418; Hypomagnesemia, seizures, and mental retardation, MONDO:0014631
Source Wessex and West Midlands GLH was added to CNNM2.
Source NHS GMS was added to CNNM2.
Sarah Leigh: Gene originally listed on the
Phenotypes for CNNM2 were set to Hypomagnesemia, seizures, and mental retardation 616418
This gene has been classified as Green List (High Evidence).
CNNM2 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review
CNNM2 was created by Sarah Leigh