Refining the 9q34.3 microduplication syndrome reveals mild neurodevelopmental features associated with a distinct global DNA methylation profile.

Autor: Rots D; Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands.; Department of Human Genetics Radboudumc, Donders Center for Medical Neuroscience, Nijmegen, The Netherlands.; Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.; Genetics Laboratory, Children's Clinical University Hospital, Riga, Latvia., Rooney K; Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, Ontario, Canada.; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada., Relator R; Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, Ontario, Canada., Kerkhof J; Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, Ontario, Canada., McConkey H; Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, Ontario, Canada.; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada., Pfundt R; Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands., Marcelis C; Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands., Willemsen MH; Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands., van Hagen JM; Department of Human Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Zwijnenburg P; Department of Human Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Alders M; Department of Human Genetics, Amsterdam Reproduction & development Research Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Õunap K; Department of Clinical Genetics, Genetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia.; Department of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia., Reimand T; Department of Clinical Genetics, Genetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia.; Department of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia., Fjodorova O; Department of Laboratory Genetics, Genetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia., Berland S; Department of Mental Health, Møre og Romsdal Hospital Trust, Ålesund, Norway., Liahjell EB; Department of Mental Health, Møre og Romsdal Hospital Trust, Ålesund, Norway., Bojovic O; Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway., Kriek M; Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands., Ruivenkamp C; Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands., Bonati MT; Department of Genetics, Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy., Brunner HG; Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands.; Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands., Vissers LELM; Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands.; Department of Human Genetics Radboudumc, Donders Center for Medical Neuroscience, Nijmegen, The Netherlands., Sadikovic B; Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, Ontario, Canada., Kleefstra T; Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands.; Department of Human Genetics Radboudumc, Donders Center for Medical Neuroscience, Nijmegen, The Netherlands.; Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2024 Jun; Vol. 105 (6), pp. 655-660. Date of Electronic Publication: 2024 Feb 21.
DOI: 10.1111/cge.14498
Abstrakt: Precise regulation of gene expression is important for correct neurodevelopment. 9q34.3 deletions affecting the EHMT1 gene result in a syndromic neurodevelopmental disorder named Kleefstra syndrome. In contrast, duplications of the 9q34.3 locus encompassing EHMT1 have been suggested to cause developmental disorders, but only limited information has been available. We have identified 15 individuals from 10 unrelated families, with 9q34.3 duplications <1.5 Mb in size, encompassing EHMT1 entirely. Clinical features included mild developmental delay, mild intellectual disability or learning problems, autism spectrum disorder, and behavior problems. The individuals did not consistently display dysmorphic features, congenital anomalies, or growth abnormalities. DNA methylation analysis revealed a weak DNAm profile for the cases with 9q34.3 duplication encompassing EHMT1, which could segregate the majority of the affected cases from controls. This study shows that individuals with 9q34.3 duplications including EHMT1 gene present with mild non-syndromic neurodevelopmental disorders and DNA methylation changes different from Kleefstra syndrome.
(© 2024 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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