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

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

doi:10.1038/s41439-021-00153-x

Takahisa Tateishi, Shiroh Miura + Show 3 more

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https://doi.org/10.1038/s41439-021-00153-x

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Journal: Human Genome Variation	Publication Date: May 25, 2021
Citations: 1	License type: open-access

Affiliation: Kurume University, Kyushu University

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.

Highlights

Spastic paraplegia (SPG) type 4 is an autosomal dominant SPG caused by functional variants in the SPAST gene
1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous disorders characterized by progressive lower-limb spasticity and weakness as a result of corticospinal dysfunction[1,2]
Correspondence: Hiroki Shibata 1Division of Genomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan 2Department of Neurology and Geriatric Medicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan Full list of author information is available at the end of the article carrying the same variant in unrelated SPG families for a final conclusion regarding the pathogenicity of the variant

Summary

Introduction

Spastic paraplegia (SPG) type 4 is an autosomal dominant SPG caused by functional variants in the SPAST gene. SPG4 is autosomal dominant and caused by functional variants in the SPAST gene, which is located at 2p22.3 and encodes the microtubule-severing protein spastin[1,4]. Kadnikova et al.[5] previously identified NM_014946.4: c.1252G>A [p.Glu418Lys] in a single Russian spastic paraplegia (SPG) family[5].

Results

Conclusion