ITPR1 variant-induced autosomal dominant hereditary spastic paraplegia in a Chinese family

TL;DR

A new genetic variant in the ITPR1 gene is linked to hereditary spastic paraplegia in a Chinese family, expanding understanding of the disease's genetic causes.

Contribution

This is the first confirmed report linking ITPR1 gene variants to autosomal dominant hereditary spastic paraplegia.

Findings

The ITPR1 variant c.2714A > G (N905S) was identified in a three-generation Chinese HSP family.

The variant is located in the coupling domain of the ITPR1 protein.

This finding expands the genetic spectrum of hereditary spastic paraplegia.

Abstract

Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disease prominently characterized by slowly progressive lower limb weakness and spasticity. The significant genotypic and phenotypic heterogeneity of this disease makes its accurate diagnosis challenging. In this study, we identified the NM_001168272: c.2714A > G (chr3.hg19: g.4716912A > G, N905S) variant in the ITPR1 gene in a three-generation Chinese family with multiple individuals affected by HSP, which we believed to be associated with HSP pathogenesis. To confirm, we performed whole exome sequencing, copy number variant assays, dynamic mutation analysis of the entire family, and protein structure prediction. The variant identified in this study was in the coupling domain, and this is the first corroborated report assigning ITPR1 variants to HSP. These findings expand the clinical and genetic spectrum of HSP and provide important data for its genetic analysis and diagnosis.

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