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Genetic epilepsy syndromes

Gene: CNKSR2

Green List (high evidence)

CNKSR2 (connector enhancer of kinase suppressor of Ras 2)
EnsemblGeneIds (GRCh38): ENSG00000149970
EnsemblGeneIds (GRCh37): ENSG00000149970
OMIM: 300724, Gene2Phenotype
CNKSR2 is in 6 panels

3 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

XL syndromic mental retardation - Houge type. Characterised by delayed development, ID, speech and lang delay and early onset seizures - some patients may have seizure remission in adolesecence. Vaags et al, 2014 - 3 adult brothers - delayed psychomotor development and seizures limited to childhood - hemizygous fs mutation identified - carried by unaff mum . Damiano et al, 2017 - family of AJ descent - variable manifestations - proband - most severely aff and onset of seizures at age 3.5 years. Brother had seizure onset at 3.5 years, sister seizure onset at 6 years and seizure free at 16. Mother had a history of febrile seizures and mothers brother had refractory seizures - hemi or het nonsense mutation identified. Cytogenetic deletions affecting the CNKSR2 gene have been reported - Houge et al, 2012, Vaags ewt al, 2015 & Aypar et al, 2015 - seizures reported in almost all aff.
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Mental retardation, X-linked, syndromic, Houge type,301008

Publications

Rebecca Foulger (Genomics England curator)

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: 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
Comment on mode of inheritance: Updated mode of inheritance from XLR to XLD based on PMID:28098945, so that affected females are detected. Damiano et al., 2017 report the first female with a CNKSR2 variant and childhood epilepsy- the sister had a less severe phenotype than her two brothers, which could be subject to X-inactivation (not directly measured). The mother, who also carries the point mutation, had only febrile seizures.
Created: 15 Jul 2019, 12:59 p.m. | Last Modified: 15 Jul 2019, 12:59 p.m.
Panel Version: 1.161

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

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 unrelated cases.
Created: 9 Apr 2018, 4:43 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Mental retardation, X-linked, syndromic, Houge type 301008

Publications

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Victorian Clinical Genetics Services
  • Expert Review Green
  • Expert Review
Phenotypes
  • Mental retardation, X-linked, syndromic, Houge type 301008
OMIM
300724
Clinvar variants
Variants in CNKSR2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to CNKSR2.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to CNKSR2.

15 Jul 2019, Gel status: 3

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: CNKSR2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

15 Jul 2019, Gel status: 3

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: CNKSR2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females

15 Jul 2019, Gel status: 3

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: CNKSR2 were set to 28098945; 25223753; 22511892

11 Dec 2018, Gel status: 4

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Sarah Leigh: Gene originally listed on the

25 Jun 2018, Gel status: 4

Added New Source

Sarah Leigh (Genomics England Curator)

Victorian Clinical Genetics Services was added to CNKSR2. Panel: Genetic Epilepsy Syndromes

9 Apr 2018, Gel status: 3

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

9 Apr 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

CNKSR2 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review

9 Apr 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

CNKSR2 was created by Sarah Leigh