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Novel SPG20 mutation in an extended family with Troyer syndrome


Troyer Syndrome (TRS) is a rare autosomal recessive complicated spastic paraplegia disorder characterized by various neurological and musculoskeletal manifestations. Pathogenicity stems from mutations in SPG20 which encodes Spartin, a multifunctional protein that is thought to be essential for neuron viability. Here we report on the clinical and molecular characterization of TRS in five patients from an extended consanguineous family in the United Arab Emirates. Molecular analysis involved Whole Exome Sequencing and Sanger sequencing for identification and confirmation of the causative variant respectively. In silico tools including CADD and Polyphen-2 were used to assess pathogenicity of the variant. The clinical description of these patients included spastic paraparesis, motor and cognitive delay, gait abnormalities, musculoskeletal features, as well as white matter abnormalities and emotional liability. Molecular analysis revealed a novel homozygous missense mutation in SPG20 (c.1324G > C; p.Ala442Pro) occurring at an evolutionarily conserved residue in the Plant-Related Senescence domain of Spartin. The mutation segregated with the clinical phenotype in all patients. In silico algorithms predict the mutation to be disease causing, and the variant had not been previously reported in public or ethnic specific variant repositories.

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Authors would like to thank patients and their families for full cooperation. Thanks also go to Dubai Health Authority and Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences for continuous and comprehensive support.


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Correspondence to S. Bizzari.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee as well as the 1964 Helsinki declaration and its later amendments.

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Authors declare that there are no conflicts of interest to report.

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Samples were obtained from patients and their parents upon informed consent.

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Bizzari, S., Hamzeh, A.R., Nair, P. et al. Novel SPG20 mutation in an extended family with Troyer syndrome. Metab Brain Dis 32, 2155–2159 (2017).

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  • Troyer syndrome
  • SPG20
  • Spartin
  • Novel mutation
  • In silico
  • United Arab Emirates