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Spiegel R, Soiferman D, Shaag A, et al. Novel Homozygous Missense Mutation in SPG20 Gene Results in Troyer Syndrome Associated with Mitochondrial Cytochrome c Oxidase Deficiency. JIMD Rep. 2016;33:55-60doi: 10.1007/8904_2016_580.
Spiegel, R., Soiferman, D., Shaag, A., Shalev, S., Elpeleg, O., & Saada, A. (2017). Novel Homozygous Missense Mutation in SPG20 Gene Results in Troyer Syndrome Associated with Mitochondrial Cytochrome c Oxidase Deficiency. JIMD reports, 3355-60. https://doi.org/10.1007/8904_2016_580
Spiegel, Ronen, et al. "Novel Homozygous Missense Mutation in SPG20 Gene Results in Troyer Syndrome Associated with Mitochondrial Cytochrome c Oxidase Deficiency." JIMD reports vol. 33 (2017): 55-60. doi: https://doi.org/10.1007/8904_2016_580
Spiegel R, Soiferman D, Shaag A, Shalev S, Elpeleg O, Saada A. Novel Homozygous Missense Mutation in SPG20 Gene Results in Troyer Syndrome Associated with Mitochondrial Cytochrome c Oxidase Deficiency. JIMD Rep. 2017;33:55-60. doi: 10.1007/8904_2016_580. Epub 2016 Aug 19. PMID: 27539578; PMCID: PMC5413448.
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JIMD Rep. 2017;33:55-60. doi: 10.1007/8904_2016_580. Epub 2016 Aug 19.

Novel Homozygous Missense Mutation in SPG20 Gene Results in Troyer Syndrome Associated with Mitochondrial Cytochrome c Oxidase Deficiency.

JIMD reports

Ronen Spiegel, Devorah Soiferman, Avraham Shaag, Stavit Shalev, Orly Elpeleg, Ann Saada

Affiliations

  1. Department of Pediatrics B, Emek Medical Center, Afula, 1834111, Israel. [email protected].
  2. Genetic Institute, Emek Medical Center, Afula, Israel. [email protected].
  3. Rappaport School of Medicine, Technion, Haifa, Israel. [email protected].
  4. Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  5. Department of Genetic and Metabolic Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  6. Genetic Institute, Emek Medical Center, Afula, Israel.
  7. Rappaport School of Medicine, Technion, Haifa, Israel.

PMID: 27539578 PMCID: PMC5413448 DOI: 10.1007/8904_2016_580

Abstract

Troyer syndrome is an autosomal recessive form of hereditary spastic paraplegia (HSP) caused by deleterious mutations in the SPG20 gene. Although the disease is associated with a loss of function mechanism of spartin, the protein encoded by SPG20, the precise pathogenesis is yet to be elucidated. Recent data indicated an important role for spartin in both mitochondrial maintenance and function. Here we report a child presenting with progressive spastic paraparesis, generalized muscle weakness, dysarthria, impaired growth, and severe isolated decrease in muscle cytochrome c oxidase (COX) activity. Whole exome sequencing identified the homozygous c.988A>G variant in SPG20 gene (p.Met330Val) resulting in almost complete loss of spartin in skeletal muscle. Further analyses demonstrated significant tissue specific reduction of COX 4, a nuclear encoded subunit of COX, in muscle suggesting a role for spartin in proper mitochondrial respiratory chain function mediated by COX activity. Our findings need to be verified in other Troyer syndrome patients in order to classify it as a form of HSP caused by mitochondrial dysfunction.

Keywords: Cytochrome c oxidase; Hereditary spastic paraplegia; Mitochondria; Oxidative phosphorylation; SPG20; Troyer syndrome

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