HUS Diagnostic Center, Division of Genetics and Clinical Pharmacology, Department of Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
HUS Diagnostic Center, Division of Genetics and Clinical Pharmacology, Laboratory of Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Mol Genet Genomic Med. 2022 Nov;10(11):e2037. doi: 10.1002/mgg3.2037. Epub 2022 Aug 18.
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.
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.
Our data add to the variety of different pathogenic variants associated with JARID2 neurodevelopmental syndrome.
最近已经证明，覆盖整个 JARID2 基因或部分基因的缺失以及导致 JARID2 单核苷酸变异体杂合功能丧失的致病性单核苷酸变异体，会导致具有明显临床特征的神经发育综合征。在这里，我们提出了一个以前未描述的 JARID2 基因部分从头重复的病例，该患者表现出与 JARID2 功能丧失变异体患者相似的特征。
该患者表现为粗大运动技能和言语发育异常以及神经精神障碍。患者有明显的眶下黑眼圈和略微突出的眶上嵴。全基因组测序和阵列比较基因组杂交显示了一种新的致病变异类型，即 JARID2 的部分串联重复，涵盖外显子 1-7。此外，RNA 测序验证了这些外显子表达增加。PRC2 复合物的靶基因也检测到表达改变，其中 JARID2 是其必需成员。
我们的数据增加了与 JARID2 神经发育综合征相关的不同致病性变异体的种类。
