Early onset or syndromic epilepsy

Gene: KMT5B

I don't know

Kept rating as Red based on Red post-Webex review from Helen Lord.

Created: 9 Sep 2019, 10:26 a.m. | Last Modified: 9 Sep 2019, 10:26 a.m.

Panel Version: 1.316

Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.

Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.

Panel Version: 1.262

Red List (low evidence)

AD MRD51 - Stessman et al, 2017 (28191889) 4 unrelated patients and reviewed 3 patients (5-7) prev reported by Iossifov et al 2014. 3 patients had a history of febrile seizures. 7 diff het variants reported Faundes et al, 2018 (29276005), 4 unrelated patients- 1 fs, 1 nonsense and 2 large deletions 2 had seizures (no info regarding type). HGMD Pro - seems to be assoc with DDD/ASD phentoype, can't see any epilepsy mentioned.

Created: 5 Sep 2019, 2:22 p.m. | Last Modified: 5 Sep 2019, 2:22 p.m.

Panel Version: 1.261

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Red List (low evidence)

KMT5B is associated with Mental retardation, autosomal dominant 51 (#617788) in OMIM and KMT5B syndrome on Gene2phenotype. This syndrome has intellectual disability and overgrowth listed as phenotypes.

PMID: 29276005 - Faundes et al 2018 - looked at patients from the Deciphering Developmental Disorders (DDD) study that high-quality-call genetic variants in methyltransferases (KMTs) and demethylases (KDMs) not yet firmly associated with DDs. 4 patients identified with either variants or deletions in KMT5B. 2 had nonsense variants, 2 had deletions encompassing KMT5B (399 kb and 839 kb). All had mild to severe intellectual disability. 2 (1 with nonsense variant, 1 with a deletion) also had seizures.
Sources: Literature

Created: 15 Jun 2019, 4:06 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Mental retardation, autosomal dominant 51, 617788

Publications

• 29276005