Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: KMT2A

The 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

Green List (high evidence)

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

• PMID: 33783954
• 28623346
• 27320412

Variants in this GENE are reported as part of current diagnostic practice

Red List (low evidence)

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

I don't know

Comment on mode of inheritance: Added MOI from external expert review

Created: 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 KMT2A

Created: 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 deficiency

Created: 17 Apr 2018, 12:29 p.m.