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A novel de novo NIPA1 missense mutation associated to hereditary spastic paraplegia

Journal of Human Genetics volume 66, pages 1177–1180 (2021)Cite this article

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Abstract

SPG6 accounts for 1% of autosomal dominant Hereditary Spastic Paraplegia (HSP) and is caused by pathogenic variants in NIPA1, which encodes a magnesium transporter located in plasma membrane and early endosomes, implicated in neuronal development and maintenance. Here we report a 39-year-old woman affected by progressive gait disturbance associated to absence seizures episodes within childhood. Clinical exome sequencing identified a likely pathogenic de novo heterozygous variant in NIPA1 (NM_144599.5 c.249 C > G; p.Asn83Lys). Molecular modelling was performed to evaluate putative functional consequence of the NIPA1 protein. Indeed, the Asn83Lys modification is predicted to induce a significant perturbation of the protein structure, altering signal transduction or small-molecule transport by modulating the length of the second transmembrane domain. This is the first study reporting a SPG6-affected patient harbouring the NIPA1 p.Asn83Lys mutation.

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Authors and Affiliations

  1. Istituto di Genetica Medica, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy

    Dora Fabbro & Giuseppe Damante

  2. Dipartimento di Area Medica, Università degli Studi di Udine, Udine, Italy

    Catia Mio & Giuseppe Damante

  3. Dipartimento di Scienze Matematiche, Informatiche e Fisiche, Università degli Studi di Udine, Udine, Italy

    Federico Fogolari

Authors
  1. Dora Fabbro
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  2. Catia Mio
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  3. Federico Fogolari
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  4. Giuseppe Damante
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Correspondence to Catia Mio.

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Fabbro, D., Mio, C., Fogolari, F. et al. A novel de novo NIPA1 missense mutation associated to hereditary spastic paraplegia. J Hum Genet 66, 1177–1180 (2021). https://doi.org/10.1038/s10038-021-00941-x

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