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SPTAN1 variants likely cause autosomal recessive complicated hereditary spastic paraplegia

Journal of Human Genetics volume 67, pages 165–168 (2022)Cite this article

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Abstract

Heterozygous mutations in SPTAN1 are associated with a broad phenotypical spectrum ranging from axonal neuropathy phenotypes to neurodevelopmental phenotypes with or without epilepsy. Recently, biallelic mutations in SPTAN1 were reported as a potential cause of autosomal recessive pure hereditary spastic paraplegia (HSP). However, no further HSP cases with biallelic SPTAN1 mutations have been reported. Herein, we report the clinical and genetic findings of a patient with complicated HSP likely caused by a novel homozygous SPTAN1 mutation. A patient with complicated HSP from a consanguineous family was recruited. The proband underwent detailed neurological examinations. Homozygosity mapping was performed in the proband and her healthy sister. Whole exome sequencing was performed in the proband. Our patient had early onset motor symptoms with upper motor neuron paralysis and intellectual disability, which is compatible with complicated HSP. Genetic analysis identified a rare homozygous missense mutation in SPTAN1 (c.4162A>G, p.I1388V), which was predicted to be deleterious by in silico tools. Her healthy parents and sister all carried the heterozygous mutation. Our results provided further support for the association of biallelic SPTAN1 variants with HSP and suggested that screening for the SPTAN1 gene should be considered not only in patients with pure HSP but also in patients with complicated HSP.

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Acknowledgements

We thank the patient and her family members for their participation.

Funding

This study was supported by the Science Technology Department of Zhejiang Province (2019C03017), the Zhejiang Province Medical and Health Technology Program (Pro. nos. 2018261205 and 2018250963).

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Authors and Affiliations

  1. Department of Neurology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

    Fei Xie

  2. Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

    Fei Xie, Shuqi Chen, Peng Liu, Xinhui Chen & Wei Luo

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  1. Fei Xie
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Correspondence to Wei Luo.

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Xie, F., Chen, S., Liu, P. et al. SPTAN1 variants likely cause autosomal recessive complicated hereditary spastic paraplegia. J Hum Genet 67, 165–168 (2022). https://doi.org/10.1038/s10038-021-00975-1

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