Intellectual disability update Jan 2018

Gene: KMT2B

Comment when marking as ready: Only one case to date presenting as ID without dystonia (the predominant phenotype). Unclear as to the clinical utility on the ID panel based upon current evidence. Considered amber and watchlist.

Created: 5 Mar 2018, 1:27 p.m.

Added watchlist tag. Building evidence for cases with moderate to severe ID (PMID: 29276005; 25405613)

Created: 27 Feb 2018, 1:15 p.m.

Comment on publications: PMID: 29289525 is a review

Created: 27 Feb 2018, 10:54 a.m.

Comment on list classification: Zech et al 2016 (PubMed:27839873) Four individuals from different families with loss-of-function variants in KMT2B and Early Onset Generalized Dystonia. Three are de novo variants. Two individuals have mild impairment of cognition and intellect. The father and grandfather of one of these two individuals also have the same KMT2B variant and show Early-onset non-generalized dystonia with mild impairment of cognition and intellect. Also found significantly decreased total mRNA levels of KMT2B in mutant fibroblasts suggesting haploinsufficiency.

Meyer et al 2016 (PMID:27992417) 27 patients with KMT2B variants. Some with several genes deleted, others with single base pair deletions or changes. Of those with only changes in KMT2B six have v. mild to moderate intellectual disability.

Fuandes et al 2018 (PMID: 29276005) report cases from Zech and Meyer plus one new patient with a de novo heterozygous variant in KMT2B and severe developmental delay/intellectual disability.

Agha et al 2014 (PMID:25405613) report a homozygous variant in KMT2B in a consanguineous family. Proband has severe intellectual disability, parents unaffected.

Created: 21 Feb 2018, 5:32 p.m.