Deep intronic deletion in intron 3 of PLP1 is associated with a severe phenotype of Pelizaeus-Merzbacher disease

Keiko Yamamoto-Shimojima; Hiroyuki Akagawa; Kumiko Yanagi; Tadashi Kaname; Nobuhiko Okamoto; Toshiyuki Yamamoto

doi:10.1038/s41439-021-00144-y

Deep intronic deletion in intron 3 of PLP1 is associated with a severe phenotype of Pelizaeus-Merzbacher disease

Hum Genome Var. 2021 Apr 1;8(1):14. doi: 10.1038/s41439-021-00144-y.

Authors

Keiko Yamamoto-Shimojima^{1

2

3}, Hiroyuki Akagawa³, Kumiko Yanagi⁴, Tadashi Kaname⁴, Nobuhiko Okamoto⁵, Toshiyuki Yamamoto^{6

7}

Affiliations

¹ Department of Transfusion Medicine and Cell Processing, Tokyo Women's Medical University, Tokyo, 162-8666, Japan.
² Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, 162-8666, Japan.
³ Tokyo Women's Medical University Institute of Integrated Medical Sciences, Tokyo, 162-8666, Japan.
⁴ Department of Genome Medicine, National Center for Child Health and Development, Tokyo, 157-8535, Japan.
⁵ Department of Medical Genetics, Osaka Women's and Children's Hospital, Osaka, Japan.
⁶ Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, 162-8666, Japan. yamamoto.toshiyuki@twmu.ac.jp.
⁷ Tokyo Women's Medical University Institute of Integrated Medical Sciences, Tokyo, 162-8666, Japan. yamamoto.toshiyuki@twmu.ac.jp.

Abstract

Recently, altered PLP1 splicing was confirmed as a genetic cause of hypomyelination of early myelinating structures (HEMS). A novel deep intronic deletion in intron 3 of PLP1 (NM_000533.5: c.453+59_+259del) was identified, and an in vitro minigene assay detected abnormal splicing patterns. However, the clinical and radiological findings of the patient were compatible with a severe phenotype of Pelizaeus-Merzbacher disease rather than HEMS, which may be due to undetected abnormal PLP1 splicing.