Relevance to Autism

De novo frameshift variants in the KMT2B were recently reported in two unrelated individuals diagnosed with autism spectrum disorder: the first was from the Children's Neurodevelopmental Center, Hasbro Children's Hospital and also presented with dysmorphic features, developmental delay/intellectual disability, and additional behavioral comorbidities, while the second was from a cohort of 112 Chinese ASD patients and their non-ASD parents from Peking University Sixth Hospital (Chang et al., 2024; Lob et al., 2024). Additional de novo variants in the KMT2B gene, incluiding a de novo nonsense variant, a de novo splice-donor variant, and five de novo missense variants, have been observed in ASD probands from the Autism Sequencing Consortium, the Simons Simplex Collection, the SPARK cohort, and the MSSNG cohort (Iossifov et al., 2014; Yuen et al., 2017; Feliciano et al., 2019; Satterstrom et al., 2020; Zhou et al., 2022; Fu et al., 2022). Heterozygous mutations in the KMT2B gene are also responsible for autosomal dominant intellectual developmental disorder 68 (MRD68; OMIM 619934) and childhood-onset dystonia 28 (DYT28; OMIM 617284). Cif et al., 2020 described a cohort of 53 patients with KMT2B mutations presenting with either dystonia (n=44) or a non-dystonic neurodevelopmental phenotype (n=9); autism spectrum disorder was reported in individuals from both subsets of KMT2B-associated disease.

Molecular Function

This gene encodes a protein which contains multiple domains including a CXXC zinc finger, three PHD zinc fingers, two FY-rich domains, and a SET (suppressor of variegation, enhancer of zeste, and trithorax) domain. The SET domain is a conserved C-terminal domain that characterizes proteins of the MLL (mixed-lineage leukemia) family. This gene is ubiquitously expressed in adult tissues.

External Links

References