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Intellectual disability

Gene: CUX2

Green List (high evidence)

CUX2 (cut like homeobox 2)
EnsemblGeneIds (GRCh38): ENSG00000111249
EnsemblGeneIds (GRCh37): ENSG00000111249
OMIM: 610648, Gene2Phenotype
CUX2 is in 6 panels

6 reviews

Sarah Leigh (Genomics England Curator)

Comment on list classification: Following personal comunication with Gemma Louise Carvill, the variant was confirmed as de novo in all nine cases mentioned in PMID 29630738.
Created: 25 Jun 2019, 8:36 a.m. | Last Modified: 25 Jun 2019, 8:36 a.m.
Panel Version: 2.884

Louise Daugherty (Genomics England Curator)

Comment on list classification: More than three unrelated individuals reported in the literature, ID is part of the phenotype. Recent publications support gene-disease association and rating of this gene to Green. In addition to Chatron et al. (2018) who describes 9 unrelated patients with early infantile epileptic encephalopathy (there is no doubt these affected cases are not unrelated), Barington et al. (2018) PMID: 29795476 describes another unrelated patient with the same variant with early infantile epileptic encephalopathy caused by the same a de novo heterozygous E590K mutation in the CUX2 gene.
Created: 31 Oct 2018, 4:59 p.m.
Comment on phenotypes: added phenotype from OMIM/MIMid and external review
Created: 31 Oct 2018, 4:56 p.m.
Comment on mode of inheritance: added MOI from publication and external review
Created: 31 Oct 2018, 4:54 p.m.
Comment on publications: added publications suggested by external reviewer which support gene-disease association and rating of this gene to Green. Intellectual disability is a prominent feature, all nine unrelated patients reported by PubMed: 29630738 had severe intellectual disability, and 7 were nonverbal.
Created: 31 Oct 2018, 4:51 p.m.

Konstantinos Varvagiannis (Other)

Green List (high evidence)

Overall 10 unrelated individuals with seizures, intellectual disability and autistic features due to a recurrent de novo missense CUX2 SNV have been reported to date. //

PMID 29630738 describes in detail the phenotype of 7 males and 2 females with the recurrent p.Glu590Lys variant (NM_015267.3:c.1768G>A). 2 of these subjects were previously published in the context of larger studies (PMID: 23020937 and 23934111). Median age at seizure onset was 6 months (2 months - 9 years). 8 of these individuals had severe cognitive impairment, while the 9th individual was to young to assess. A few of these individuals were seizure-free at the time of inclusion while 4 (of the 9) individuals were identified by screening patient cohorts with intellectual disability with/without epilepsy (as in the case of PMID 23020937). As a result inclusion in the intellectual disability gene panel is also relevant despite epilepsy being commonly (but not always) the presenting feature. //

PMID 29795476 reports on a further individual with intellectual disability, seizures and ASD due to the de novo occurrence of the same variant. There are no shared authors between this article and PMID 29630738. //

As a result this gene could be considered for inclusion in this panel as green (or amber).
Created: 19 Aug 2018, 12:10 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)

Phenotypes
Seizures; Intellectual disability; Autistic behavior

Publications

Caroline Wright (Sanger)

Red List (low evidence)

Ellen McDonagh (Genomics England Curator)

Red List (low evidence)

Expressed in the brain. Role in dendritogenesis and synaptogenesis. Candidate gene for ID in PMID: 26350204. No published cases related to ID and variants in this gene identified.
Created: 27 Oct 2017, 2:46 p.m.

Publications

Lu Raymond (university of cambridge )

Red List (low evidence)

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Sources
  • Expert Review Green
Phenotypes
  • Epileptic encephalopathy, early infantile, 67, 618141
  • Seizures
  • Intellectual disability
  • Autistic behavior
OMIM
610648
Clinvar variants
Variants in CUX2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

25 Jun 2019, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: cux2 has been classified as Green List (High Evidence).

31 Oct 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: cux2 has been classified as Green List (High Evidence).

31 Oct 2018, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: CUX2 were changed from to Epileptic encephalopathy, early infantile, 67, 618141; Seizures; Intellectual disability; Autistic behavior

31 Oct 2018, Gel status: 1

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: CUX2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)

31 Oct 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: CUX2 were set to 21331220; 26350204

12 Mar 2018, Gel status: 1

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

29 Nov 2017, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for gene CUX2 was set to ['21331220', '26350204']

13 Nov 2015, Gel status: 1

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

CUX2 was created by ellenmcdonagh

13 Nov 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

CUX2 was added to Intellectual disabilitypanel. Sources: Expert Review Red