Intellectual disability
Gene: CUX2Comment on mode of inheritance: Changed MOI from 'Monoallelic... paternally imprinted (maternal allele expressed)' to 'Monoallelic... NOT imprinted', in line with Tracy Lester's recent review highlighting there is no evidence of imprinting in this gene.Created: 8 Jul 2021, 9:40 a.m. | Last Modified: 8 Jul 2021, 9:40 a.m.
Panel Version: 3.1164
Recurrent de novo missense variant - no evidence that this gene is imprinted. Please amend the mode of inheritanceCreated: 29 Jun 2021, 11:19 a.m. | Last Modified: 29 Jun 2021, 11:19 a.m.
Panel Version: 3.1149
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of pathogenicity
Other
Variants in this GENE are reported as part of current diagnostic practice
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
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 reviewCreated: 31 Oct 2018, 4:56 p.m.
Comment on mode of inheritance: added MOI from publication and external reviewCreated: 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.
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
Tag Q3_21_NHS_review tag was added to gene: CUX2.
Mode of inheritance for gene: CUX2 was changed from MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CUX2 were changed from Epileptic encephalopathy, early infantile, 67, 618141; Seizures; Intellectual disability; Autistic behavior to Developmental and epileptic encephalopathy 67, OMIM:618141; Seizures; Intellectual disability; Autistic behaviour
Gene: cux2 has been classified as Green List (High Evidence).
Gene: cux2 has been classified as Green List (High Evidence).
Phenotypes for gene: CUX2 were changed from to Epileptic encephalopathy, early infantile, 67, 618141; Seizures; Intellectual disability; Autistic behavior
Mode of inheritance for gene: CUX2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: CUX2 were set to 21331220; 26350204
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.
Publications for gene CUX2 was set to ['21331220', '26350204']
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
CUX2 was created by ellenmcdonagh
CUX2 was added to Intellectual disabilitypanel. Sources: Expert Review Red