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A novel frameshift deletion in in a patient with Kleefstra Syndrome results in decreased H3K9 dimethylation. Mol Genet Genomic Med 2017 Mar;5(2):141-146 PMID: 28361100 PMCID: PMC5370226

Pubmed ID





BACKGROUND: Kleefstra Syndrome (KS) (MIM# 610253) is an autosomal dominant disorder caused by haploinsufficiency of euchromatic histone methyltransferase-1 ( GLP). (MIM# 607001) encodes a histone methyltransferase that heterodimerizes with EHMT2 (also known as G9a, MIM# 604599), which together are responsible for mono- and dimethylation of H3 lysine 9 (H3K9me1 and -me2), resulting in transcriptional repression of target genes.

METHODS: This report describes an 18-year-old woman with intellectual disability, severely limited speech, hypotonia, microcephaly, and facial dysmorphisms, who was found to have a novel single-base frameshift deletion in .

RESULTS: Functional studies using patient fibroblasts showed decreased H3K9me2 compared to wild-type control cells, thus providing a rapid confirmatory test that complements molecular studies.

CONCLUSION: Whole exome sequencing revealed a novel frameshift deletion in after a lengthy diagnostic odyssey in this patient. Functional testing using this patient's fibroblasts provides proof-of-concept for the analysis of variants of uncertain significance that are predicted to impact EHMT1 enzymatic activity.

Author List

Blackburn PR, Williams M, Cousin MA, Boczek NJ, Beek GJ, Lomberk GA, Urrutia RA, Babovic-Vuksanovic D, Klee EW


Gwen Lomberk PhD Associate Professor in the Surgery department at Medical College of Wisconsin
Raul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin

jenkins-FCD Prod-310 bff9d975ec7f2d302586822146c2801dd4449aad