Intellectual disability
Gene: KDM5AThis gene is not currently associated with a disease phenotype in OMIM, but checked PMID:33350388 to make sure it is the same gene listed in the publication as on this panel and it is, so added the gene-checked tagCreated: 16 Oct 2023, 7:44 p.m. | Last Modified: 16 Oct 2023, 7:44 p.m.
Panel Version: 5.313
The rating of this gene has been updated to Green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, 9:34 a.m. | Last Modified: 11 Oct 2023, 9:34 a.m.
Panel Version: 5.286
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Comment on list classification:, There is sufficient evidence for this gene to be promoted to GREEN at the next major review.
This gene can be associated with both monoallelic and biallelic inheritance as there are at least three cases each for both of them.Created: 11 Apr 2023, 4:52 p.m. | Last Modified: 11 Apr 2023, 5:11 p.m.
Panel Version: 5.25
PMID:21937992 reported a family with recessive missense KDM5A variant presenting with an undefined developmental disorder characterised with intellectual disability and facial dysmorphisms.
PMID:33350388 reported nine patients from seven unrelated families identified with variants in KDM5A, of which three unrelated patients harboured heterozygous variants, while six patients from four unrelated families had homozygous variants. These patients presented with autism spectrum disorder (ASD) and a spectrum of neurodevelopmental phenotypes including intellectual disability, lack of speech, developmental delay and motor impairment.
In addition, loss of KDM5A has resulted in repetitive behaviors, sociability deficits, cognitive dysfunction, and abnormal dendritic morphogenesis in mice.
This gene has already been associated with phenotype in Gene2Phenotype (biallelic inheritance with 'limited' rating), but not in OMIM.Created: 11 Apr 2023, 3:42 p.m. | Last Modified: 11 Apr 2023, 5:05 p.m.
Panel Version: 5.24
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071
Publications
El Hayek et al (2020) PMID:33350388: We utilized a forward genetics approach to rapidly identify new mutations causing ASD-related behaviors in mice. We screened mice bearing N-ethyl-N-nitrosourea (ENU)-induced mutations (Wang et al., 2015) for defects in ultrasonic vocalizations (USVs) and nest-building behavior. Automated meiotic mapping implicated Kdm5a as a candidate ASD gene and a nonsense mutation at that locus segregated with defective USVs and nest building. In addition to these phenotypes, targeted knockout of Kdm5a resulted in repetitive behaviors, deficits in social interaction, learning, and memory, and abnormal neuronal morphology. KDM5A encodes a chromatin regulator that belongs to the KDM5 family of lysine-specific histone H3 demethylases. Histone H3 lysine 4 trimethyl (H3K4me3) marks are present at gene promoters and active enhancers, and are regulated by multiple factors, including the KDM5 family members KDM5B and KDM5C (Shen et al., 2017). Mutations in lysine demethylases that regulate the demethylation of the H3K4me3 marks have been strongly linked to a host of neurodevelopmental disorders. Finally, we identified nine patients with ASD and lack of speech who have pathogenic KDM5A variants.
7 families were reported, 3 consanguineous with hom del ex6-9, c.2541+1G>T, F477V. and 4 isolated cases - 3 het de novo (p.M1?, R1428L, R1350*) and 1 with AR del ex1-10
Might be sufficient evidence to upgrade this gene to green for both AR and AD ID?Created: 28 Mar 2023, 1:45 p.m. | Last Modified: 28 Mar 2023, 1:45 p.m.
Panel Version: 5.11
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
ASD, lack of speech
Publications
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
AUTOSOMAL RECESSIVE MENTAL RETARDATION
Publications
Should be grey. ]No evidence to suggest that variants in this gene are linked to Intellectual Disability. However, there is some evidence linking fusion variants in this gene to poor prognosis in megakaryoblastic leukaemiaCreated: 31 Oct 2017, 10:36 a.m.
Mode of inheritance
Unknown
Phenotypes for gene: KDM5A were changed from autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071; El Hayek-Chahrour neurodevelopmental syndrome, OMIM:620820
Tag gene-checked was removed from gene: KDM5A.
Tag gene-checked tag was added to gene: KDM5A.
Phenotypes for gene: KDM5A were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071
Tag Q2_23_promote_green was removed from gene: KDM5A. Tag Q2_23_NHS_review was removed from gene: KDM5A.
Source NHS GMS was added to KDM5A. Source Expert Review Green was added to KDM5A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q2_23_NHS_review tag was added to gene: KDM5A.
Tag Q2_23_promote_green tag was added to gene: KDM5A.
Phenotypes for gene: KDM5A were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071
Phenotypes for gene: KDM5A were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071
Phenotypes for gene: KDM5A were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071
Phenotypes for gene: KDM5A were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071
Gene: kdm5a has been classified as Amber List (Moderate Evidence).
Publications for gene: KDM5A were set to 21937992; 33350388
Publications for gene: KDM5A were set to 21937992; 33350388
Publications for gene: KDM5A were set to 21937992; 33350388
Publications for gene: KDM5A were set to 21937992; 33350388
Publications for gene: KDM5A were set to 21937992; 33350388
Publications for gene: KDM5A were set to 21937992; 33350388
Publications for gene: KDM5A were set to 21937992; 33350388
Publications for gene: KDM5A were set to 21937992; 33350388
Publications for gene: KDM5A were set to 21937992; 33350388
Publications for gene: KDM5A were set to 21937992; 33350388
Publications for gene: KDM5A were set to 21937992; 33350388
Publications for gene: KDM5A were set to 21937992; 33350388
Publications for gene: KDM5A were set to 21937992; 33350388
Publications for gene: KDM5A were set to 21937992; 33350388
Publications for gene: KDM5A were set to 21937992; 33350388
Publications for gene: KDM5A were set to 21937992
Mode of inheritance for gene: KDM5A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mode of inheritance for gene: KDM5A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mode of inheritance for gene: KDM5A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mode of inheritance for gene: KDM5A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mode of inheritance for gene: KDM5A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
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.
Model of inheritance for gene KDM5A was set to Unknown
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
KDM5A was added to Intellectual disabilitypanel. Sources: Expert Review Red
KDM5A was created by ellenmcdonagh