{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:40:20Z","timestamp":1791214820145,"version":"4.1.0"},"reference-count":37,"publisher":"BMJ","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2012,10,5]]},"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Autosomal recessive hereditary spastic paraplegias (AR-HSP) constitute a heterogeneous group of neurodegenerative diseases involving pyramidal tracts dysfunction. The genes responsible for many types of AR-HSPs remain unknown. We attempted to identify the gene responsible for AR-HSP with optic atrophy and neuropathy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The present study involved two patients in a consanguineous Japanese family. Neurologic examination and DNA analysis were performed for both patients, and a skin biopsy for one. We performed genome-wide linkage analysis involving single nucleotide polymorphism arrays, copy-number variation analysis, and exome sequencing. To clarify the mitochondrial functional alteration resulting from the identified mutation, we performed immunoblot analysis, mitochondrial protein synthesis assaying, blue native polyacrylamide gel electrophoresis (BN-PAGE) analysis, and respiratory enzyme activity assaying of cultured fibroblasts of the patient and a control.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified a homozygous nonsense mutation (c.394C&gt;T, p.R132X) in <jats:italic>C12orf65<\/jats:italic> in the two patients in this family. This <jats:italic>C12orf65<\/jats:italic> mutation was not found in 74 Japanese AR-HSP index patients without any mutations in previously known HSP genes. This mutation resulted in marked reduction of mitochondrial protein synthesis, followed by functional and structural defects in respiratory complexes I and IV.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This novel nonsense mutation in <jats:italic>C12orf65<\/jats:italic> could cause AR-HSP with optic atrophy and neuropathy, resulting in a premature stop codon. The truncated <jats:italic>C12orf65<\/jats:italic> protein must lead to a defect in mitochondrial protein synthesis and a reduction in the respiratory complex enzyme activity. Thus, dysfunction of mitochondrial translation could be one of the pathogenic mechanisms underlying HSPs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmedgenet-2012-101212","type":"journal-article","created":{"date-parts":[[2012,11,27]],"date-time":"2012-11-27T05:08:35Z","timestamp":1353992915000},"page":"777-784","source":"Crossref","is-referenced-by-count":81,"title":["A homozygous mutation of <i>C12orf65<\/i> causes spastic paraplegia with optic atrophy and neuropathy (SPG55)"],"prefix":"10.1136","volume":"49","author":[{"given":"Haruo","family":"Shimazaki","sequence":"first","affiliation":[{"name":"Division of Neurology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihisa","family":"Takiyama","sequence":"additional","affiliation":[{"name":"Department of Neurology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, 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