Intellectual disability - microarray and sequencing
Gene: KDM1A
Mouse studies are available detailing deletions in this gene - which were found to be lethal. PMID 26077434 notes that only one KDM1A variant has been described in a developmental disorder so far, but it does not detail this finding. In PMID 24838796, one case is described in a patient with a variant in this gene along with a variant in ANKRD11. The phenotypes listed include clefting, hypospadias and choradee, patent foramen ovale, global developmental delay and hypotonia. The authors of the paper hypothesise that both variants are contributing to the patient's overall disorder phenotype.Created: 31 Oct 2017, 10:36 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Cleft palate, psychomotor retardation, and distinctive facial features
Publications
As a result of watchlist tag audit the watchlist tag was removed from KDM1A- this is now a green gene with sufficient evidence/reviewCreated: 13 Jan 2020, 3:40 p.m. | Last Modified: 13 Jan 2020, 3:40 p.m.
Panel Version: 3.0
Comment on list classification: Changed from Red to Green. Publications support gene-disease association and rating of this gene to Green on the ID panelCreated: 27 Sep 2018, 4:07 p.m.
Comment on list classification: Changed from Red to Green. Publications support gene-disease association and rating of this gene to Green on the ID panelCreated: 27 Sep 2018, 4:04 p.m.
Comment on phenotypes: added MIMidCreated: 27 Sep 2018, 3:59 p.m.
Recommendation that this gene should be Green. Three patients https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902791/, there is functional characterisation of the three described mutations https://www.ncbi.nlm.nih.gov/pubmed/27094131?dopt=Abstract and the patients seem to share a similar phenotype, which recapitulates features of other deleterious mutations in better-characterised lysine demethylase and chromatin remodelling genes. There is also a recurrent de novo variant p.Tyr831Cys which has been reported in two separate "autism spectrum" patients in large cohort studies. The gene is also extensively constrained against both missense and LOF variation in humans http://exac.broadinstitute.org/gene/ENSG00000004487. I think what's been reported so far is probably robust enough to use the gene clinically.Pers comm. Ian Berry (NHS Leeds Genetics Laboratory)Created: 27 Sep 2018, 3:55 p.m.
Comment on publications: Three unrelated cases for the disorder: Cleft palate, psychomotor retardation, and distinctive facial features, this would suggest the status for this gene is changed from Red to Green. The finding of the second and third unrelated cases are in a paper published August 2016 (PMID: 26656649), which is after this gene on this panel was reviewed by experts in February 2016, both reviewed the gene and denoted the evidence as being low (Red), likely due to not enough published evidence at the time. Need to recheck with reviewers.Created: 27 Jan 2017, 1:30 p.m.
Tag watchlist was removed from gene: KDM1A.
Source Victorian Clinical Genetics Services was added to KDM1A.
Phenotypes for gene: KDM1A were changed from Cleft palate, psychomotor retardation, and distinctive facial features, 616728 to Cleft palate, psychomotor retardation, and distinctive facial features, 616728; Developmental delay
Gene: kdm1a has been classified as Green List (High Evidence).
Gene: kdm1a has been classified as Green List (High Evidence).
Gene: kdm1a has been classified as Green List (High Evidence).
Publications for gene: KDM1A were set to 26077434; 24838796
Phenotypes for gene: KDM1A were changed from Cleft palate, psychomotor retardation, and distinctive facial features to Cleft palate, psychomotor retardation, and distinctive facial features, 616728
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 KDM1A was set to ['26077434', ' 24838796']
Publications for KDM1A were set to 24838796; 26656649; 23020937
Mode of inheritance for KDM1A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mode of inheritance for KDM1A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for KDM1A were set to 24838796; 26656649; 23020937;
KDM1A was added to Intellectual disabilitypanel. Sources: Radboud University Medical Center, Nijmegen
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
KDM1A was added to Intellectual disabilitypanel. Sources: Expert Review Red
KDM1A was created by ellenmcdonagh