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. 2024 Jun;105(6):655-660.
doi: 10.1111/cge.14498. Epub 2024 Feb 21.

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

Dmitrijs Rots  1   2   3   4 , Kathleen Rooney  5   6 , Raissa Relator  5 , Jennifer Kerkhof  5 , Haley McConkey  5   6 , Rolph Pfundt  1 , Carlo Marcelis  1 , Marjolein H Willemsen  1 , Johanna M van Hagen  7 , Petra Zwijnenburg  7 , Marielle Alders  8 , Katrin Õunap  9   10 , Tiia Reimand  9   10 , Olga Fjodorova  11 , Siren Berland  12 , Eva Benedicte Liahjell  12 , Ognjen Bojovic  13 , Marjolein Kriek  14 , Claudia Ruivenkamp  14 , Maria Teresa Bonati  15 , Han G Brunner  1   16 , Lisenka E L M Vissers  1   2 , Bekim Sadikovic  5 , Tjitske Kleefstra  1   2   3
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Refining the 9q34.3 microduplication syndrome reveals mild neurodevelopmental features associated with a distinct global DNA methylation profile

Dmitrijs Rots et al. Clin Genet. 2024 Jun.

Abstract

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.

Keywords: 9q34.3 duplication; DNA methylation; EHMT1; neurodevelopmental disorder.

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References

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