A novel partial de novo duplication of JARID2 gene causing a neurodevelopmental phenotype

BACKGROUND: Deletions covering the entire or partial JARID2 gene as well as pathogenic single nucleotide variants leading to haploinsufficiency of JARID2 have recently been shown to cause a clinically distinct neurodevelopmental syndrome. Here, we present a previously undescribed partial de novo duplication of the JARID2 gene in a patient displaying features similar to those of patients with JARID2 loss‐of‐function variants. CASE REPORT: The index patient presents with abnormalities in gross motor skills and speech development as well as neuropsychiatric disorders. The patient has markedly dark infraorbital circles and slightly prominent supraorbital ridges.Whole‐genome sequencing and array comparative genomic hybridization revealed a novel disease‐causing variant type, a partial tandem duplication of JARID2, covering the exons 1–7. Furthermore, RNA sequencing validated the increased expression of these exons. Expression alterations were also detected in target genes of the PRC2 complex, in which JARID2 acts as an essential member. CONCLUSION: Our data add to the variety of different pathogenic variants associated with JARID2 neurodevelopmental syndrome.