9q34.3 microduplications lead to neurodevelopmental disorders through EHMT1 overexpression

Maria Teresa Bonati, Chiara Castronovo, Alessandra Sironi, Dario Zimbalatti, Ilaria Bestetti, Milena Crippa, Antonio Novelli, Sara Loddo, Maria Lisa Dentici, Juliet Taylor, Françoise Devillard, Lidia Larizza, Palma Finelli

Research output: Contribution to journalArticlepeer-review


Both copy number losses and gains occur within subtelomeric 9q34 region without common breakpoints. The microdeletions cause Kleefstra syndrome (KS), whose responsible gene is EHMT1. A 9q34 duplication syndrome (9q34 DS) had been reported in literature, but it has never been characterized by a detailed molecular analysis of the gene content and endpoints. To the best of our knowledge, we report on the first patient carrying the smallest 9q34.3 duplication containing EHMT1 as the only relevant gene. We compared him with 21 reported patients described here as carrying 9q34.3 duplications encompassing the entire gene and extending within ~ 3 Mb. By surveying the available clinical and molecular cytogenetic data, we were able to discover that similar neurodevelopmental disorders (NDDs) were shared by patient carriers of even very differently sized duplications. Moreover, some facial features of the 9q34 DS were more represented than those of KS. However, an accurate in silico analysis of the genes mapped in all the duplications allowed us to support EHMT1 as being sufficient to cause a NDD phenotype. Wider patient cohorts are needed to ascertain whether the rearrangements have full causative role or simply confer the susceptibility to NDDs and possibly to identify the cognitive and behavioral profile associated with the increased dosage of EHMT1.

Original languageEnglish
Publication statusE-pub ahead of print - Jun 17 2019


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