Novel de novo SPAST mutation in a Han Chinese SPG4 patient: a case report

TL;DR

A new mutation in the SPAST gene was found in a Han Chinese patient with spastic paraplegia type 4, suggesting it arose spontaneously and contributes to the disease's genetic diversity.

Contribution

A novel de novo SPAST mutation is reported, expanding the known genetic spectrum of SPG4 and highlighting its potential for late-onset disease.

Findings

A de novo frameshift variant, c.1545dupA, was identified in the SPAST gene of a Han Chinese SPG4 patient.

The mutation was absent in the patient's asymptomatic parents, confirming its de novo origin.

The case demonstrates that de novo SPAST mutations can present as late-onset pure SPG4 without family history.

Abstract

Spastic paraplegia type 4 (SPG4), the predominant form of Autosomal Dominant Hereditary spastic paraplegia (AD-HSP), is characterized by variants in the SPAST gene. This study reports a unique case of a late-onset SPG4 in a Han Chinese male, manifesting primarily as gait disturbances from lower extremity spasticity. Uncovered through whole-genome sequencing, a previously undocumented frameshift variant, c.1545dupA in exon 14 of the SPAST gene, was identified. Notably, this variant was absent in asymptomatic parents with confirmed paternity and maternity status, suggesting a de novo variant occurrence. This discovery emphasizes the potential of de novo variants to exhibit a late-onset pure pattern, extending the SPG4 variant spectrum, and consideration of such variants should be given in HSP patients with a negative family history.

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