TY - JOUR
T1 - Refining the 9q34.3 microduplication syndrome reveals mild neurodevelopmental features associated with a distinct global DNA methylation profile
AU - Rots, Dmitrijs
AU - Rooney, Kathleen
AU - Relator, Raissa
AU - Kerkhof, Jennifer
AU - McConkey, Haley
AU - Pfundt, Rolph
AU - Marcelis, Carlo
AU - Willemsen, Marjolein H
AU - van Hagen, Johanna M
AU - Zwijnenburg, Petra
AU - Alders, Marielle
AU - Õunap, Katrin
AU - Reimand, Tiia
AU - Fjodorova, Olga
AU - Berland, Siren
AU - Liahjell, Eva Benedicte
AU - Bojovic, Ognjen
AU - Kriek, Marjolein
AU - Ruivenkamp, Claudia
AU - Bonati, Maria Teresa
AU - Brunner, Han G
AU - Vissers, Lisenka E L M
AU - Sadikovic, Bekim
AU - Kleefstra, Tjitske
PY - 2024/2/21
Y1 - 2024/2/21
N2 - 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.
AB - 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.
KW - 9q34.3 duplication
KW - DNA methylation
KW - EHMT1
KW - neurodevelopmental disorder
U2 - 10.1111/cge.14498
DO - 10.1111/cge.14498
M3 - Article
SN - 0009-9163
JO - Clinical Genetics
JF - Clinical Genetics
ER -