Abstract
Background: Kleefstra Syndrome (KS) (MIM# 610253) is an autosomal dominant disorder caused by haploinsufficiency of euchromatic histone methyltransferase-1 (EHMT1, GLP). EHMT1 (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 de novo single-base frameshift deletion in EHMT1. 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 EHMT1 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.
Original language | English (US) |
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Pages (from-to) | 141-146 |
Number of pages | 6 |
Journal | Molecular Genetics and Genomic Medicine |
Volume | 5 |
Issue number | 2 |
DOIs | |
State | Published - Mar 2017 |
Keywords
- EHMT1
- GLP
- Kleefstra Syndrome
- functional validation
- p.Arg310Aspfs*4
- whole exome sequencing
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Genetics(clinical)