A novel DLG4 variant causes DLG4-related synaptopathy with intellectual regression

Sachi Tokunaga; Hideki Shimomura; Naoko Taniguchi; Kumiko Yanagi; Tadashi Kaname; Nobuhiko Okamoto; Yasuhiro Takeshima

doi:10.1038/s41439-023-00260-x

A novel DLG4 variant causes DLG4-related synaptopathy with intellectual regression

Hum Genome Var. 2024 Jan 5;11(1):1. doi: 10.1038/s41439-023-00260-x.

Authors

Sachi Tokunaga¹, Hideki Shimomura², Naoko Taniguchi², Kumiko Yanagi³, Tadashi Kaname³, Nobuhiko Okamoto⁴, Yasuhiro Takeshima²

Affiliations

¹ Department of Pediatrics, Hyogo Medical University School of Medicine, Nishinomiya, Hyogo, Japan. sa-tokunaga@hyo-med.ac.jp.
² Department of Pediatrics, Hyogo Medical University School of Medicine, Nishinomiya, Hyogo, Japan.
³ Department of Genome Medicine, National Center for Child Health and Development, Tokyo, Japan.
⁴ Department of Medical Genetics, Osaka Women's and Children's Hospital, Osaka, Japan.

Abstract

DLG4-related synaptopathy is a neurodevelopmental disorder caused by a DLG4 variant. We identified a novel de novo heterozygous frameshift variant, NM_001321075.3(DLG4):c.554_563del, in a Japanese girl. Intellectual regression without motor delay was observed at 2 years of age, and she was diagnosed with autism spectrum disorder and attention-deficit/hyperactivity disorder. Recognizing the possibility of DLG4-related synaptopathy in patients with intellectual regression is important for ensuring an accurate diagnosis.