Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: KMT2AThe rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 8 Mar 2022, 10:59 a.m. | Last Modified: 8 Mar 2022, 10:59 a.m.
Panel Version: 2.532
Comment on list classification: Upgraded from Red to Amber but there is enough evidence to promote to Green at the next GMS panel update.
Immune dysfunction, including early-onset CVID and recurrent infections, have been reported in multiple individuals with Wiedemann-Steiner syndrome. Immunopathology can be a presenting feature, and as there are sufficient unrelated cases with this phenotype, this gene should be promoted to Green.Created: 29 Sep 2021, 11:52 a.m. | Last Modified: 29 Sep 2021, 11:52 a.m.
Panel Version: 2.475
Multiple individuals reported in the literature with hypogammaglobulinemia:
1) Two siblings in 28623346;
2) case in 27320412
3) Multiple individuals in a large review 33783954. "Thirteen participants completed immunology laboratory evaluations. Seven participants (53.8%) had abnormal immunoglobulin levels. Four participants (30.8%) had insufficient response to pneumococcal vaccinations. There were 18 participants (25.7%) with recurrent infections."
Therefore, immunological abnormaliteis and infections are common among WSS patients.
Additionally, KMT2A is included in IEI classification PMID: 31953710.Created: 24 Sep 2021, 12:31 p.m. | Last Modified: 24 Sep 2021, 12:31 p.m.
Panel Version: 2.468
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Hypogammaglobulinemia; intellectual disability; hypertrichosis
Publications
Variants in this GENE are reported as part of current diagnostic practice
Poor evidence for any pathogenic link to immunodeficiency (single case report of immunodeficiency in a child with Wiedemann-Steiner syndrome and KMT2A mutation)Created: 11 Jun 2018, 1:39 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Comment on mode of inheritance: Added MOI from external expert reviewCreated: 12 Jun 2018, 4:52 p.m.
Gene kept Red, external expert review supports Red status due to only one case reported, that has poor evidence for any pathogenic link to immunodeficiency.Created: 12 Jun 2018, 4:46 p.m.
Comment on phenotypes: added phenotype from PMID: 27320412. Currently only one reported case in the literature with this observed phenotype caused by KMT2ACreated: 31 May 2018, 10:45 a.m.
Comment on publications: added publication to support PID phenotype. Missense variant reported.Created: 31 May 2018, 10:44 a.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: 11q23, PanelApp HGNC gene symbol check: KMT2A, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Predominantly antibody disorders / Unclassified antibody deficiency / Unclassified antibody deficiencyCreated: 17 Apr 2018, 12:29 p.m.
Tag Q3_21_rating was removed from gene: KMT2A.
Source Expert Review Green was added to KMT2A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: kmt2a has been classified as Amber List (Moderate Evidence).
Publications for gene: KMT2A were set to 32048120; 27320412; 32086639
Tag Q3_21_rating tag was added to gene: KMT2A.
Phenotypes for gene: KMT2A were changed from Wiedemann-Steiner syndrome with Congenital immunodeficiency; Unclassified antibody deficiency; Respiratory infections, short stature, hypertelorism, hairy elbows, developmental delay, intellectual disability; Combined immunodeficiencies with associated or syndromic features to Wiedemann-Steiner syndrome, OMIM:605130
Source IUIS Classification December 2019 was added to KMT2A. Added phenotypes Respiratory infections, short stature, hypertelorism, hairy elbows, developmental delay, intellectual disability; Combined immunodeficiencies with associated or syndromic features for gene: KMT2A Publications for gene KMT2A were updated from 27320412 to 32048120; 27320412; 32086639
2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.
Mode of inheritance for gene: KMT2A was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Gene: kmt2a has been classified as Red List (Low Evidence).
Publications for gene: KMT2A were set to 27320412
Phenotypes for gene: KMT2A were set to Unclassified antibody deficiency; Wiedemann-Steiner syndrome with Congenital immunodeficiency
Publications for gene: KMT2A were set to 27320412
Publications for gene: KMT2A were set to 27320412
KMT2A was added to Primary immunodeficiency disorders panel. Sources: ESID Registry 20171117
KMT2A was created by Louise Daugherty