A Japanese hereditary spastic paraplegia family with a rare nonsynonymous variant in the SPAST gene

Takuya Morikawa; Shiroh Miura; Takahisa Tateishi; Kazuhito Noda; Hiroki Shibata

doi:10.1038/s41439-021-00153-x

A Japanese hereditary spastic paraplegia family with a rare nonsynonymous variant in the SPAST gene

Hum Genome Var. 2021 May 25;8(1):21. doi: 10.1038/s41439-021-00153-x.

Authors

Takuya Morikawa¹, Shiroh Miura², Takahisa Tateishi³, Kazuhito Noda⁴, Hiroki Shibata⁵

Affiliations

¹ Division of Genomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan.
² Department of Neurology and Geriatric Medicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
³ Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahimachi, Kurume, Japan.
⁴ Nodakousei Clinic, 5-4, Kurihara, Ogi, Japan.
⁵ Division of Genomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan. hshibata@gen.kyushu-u.ac.jp.

Abstract

Spastic paraplegia (SPG) type 4 is an autosomal dominant SPG caused by functional variants in the SPAST gene. We examined a Japanese family with three autosomal dominant SPG patients. These patients presented with typical symptoms of SPG, such as spasticity of the lower limbs. We identified a rare nonsynonymous variant, NM_014946.4:c.1252G>A [p.Glu418Lys], in all three family members. This variant has previously been reported in a Russian SPG family as a "likely pathogenic" variant.⁵ Ascertainment of additional patients carrying this variant in an unrelated Japanese SPG family further supports its pathogenicity. Molecular diagnosis of SPG4 in this family with hereditary spastic paraplegia is confirmed.