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

Dmitrijs Rots, Kathleen Rooney, Raissa Relator, Jennifer Kerkhof, Haley McConkey, Rolph Pfundt, Carlo Marcelis, Marjolein H. Willemsen, Johanna M. van Hagen, Petra Zwijnenburg, Marielle Alders, Katrin Õunap, Tiia Reimand, Olga Fjodorova, Siren Berland, Eva Benedicte Liahjell, Ognjen Bojovic, Marjolein Kriek, Claudia Ruivenkamp, Maria Teresa BonatiHan G. Brunner, Lisenka E. L. M. Vissers, Bekim Sadikovic, Tjitske Kleefstra

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)655-660
Number of pages6
JournalClinical genetics
Issue number6
Early online date2024
Publication statusPublished - Jun 2024


  • 9q34.3 duplication
  • DNA methylation
  • EHMT1
  • neurodevelopmental disorder

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