{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:40:10Z","timestamp":1790098810592,"version":"4.0.1"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T00:00:00Z","timestamp":1680480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Hereditary spastic paraplegias (HSP) are inherited neurodegenerative disorders characterized by progressive paraplegia and spasticity in the lower limbs. SPG48 represents a rare genotype characterized by mutations in <jats:italic>AP5Z1<\/jats:italic>, a gene playing a role in intracellular membrane trafficking. This study describes a case of a 53-year-old male patient with SPG48 presenting spastic paraplegia, infertility, hearing impairment, cognitive abnormalities and peripheral neuropathy. The Sanger sequencing revealed a homozygous deletion in the chr 7:4785904-4786677 region causing a premature stop codon in exon 10. The patient's brother was heterozygous for the mutation. The brain magnetic resonance imaging found a mild brain atrophy and white matter lesions. In the analysis of the auditory thresholds, we found a significant hearing decrease in both ears.<\/jats:p>","DOI":"10.3389\/fneur.2023.1156100","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T04:29:17Z","timestamp":1680496157000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Hereditary spastic paraplegia (SPG 48) with deafness and azoospermia: A case report"],"prefix":"10.3389","volume":"14","author":[{"given":"Ping","family":"Jin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Nian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gong-Qiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ming","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1002\/mgg3.87","article-title":"AP5Z1\/SPG48 frequency in autosomal recessive and sporadic spastic paraplegia","volume":"2","author":"Schlipf","year":"2014","journal-title":"Mol Genet Genomic Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.neurol.2015.02.017","article-title":"Clinical and genetic heterogeneity in hereditary spastic paraplegias: from SPG1 to SPG72 and still counting","volume":"171","author":"Klebe","year":"2015","journal-title":"Rev Neurol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"543","DOI":"10.5692\/clinicalneurol.60.cn-001419","article-title":"A case of spastic paraplegia 48 with a novel mutation in the AP5Z1 gene","volume":"60","author":"Maruta","year":"2020","journal-title":"Rinsho Shinkeigaku."},{"key":"B4","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s40035-019-0157-9","article-title":"Clinical features and genetic spectrum in Chinese patients with recessive hereditary spastic paraplegia","volume":"8","author":"Wei","year":"2019","journal-title":"Transl Neurodegener."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e1000408","DOI":"10.1371\/journal.pbio.1000408","article-title":"A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia","volume":"8","author":"S\u0142abicki","year":"2010","journal-title":"PLoS Biol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1083\/jcb.201208152","article-title":"The cell biology of disease: lysosomal storage disorders: the cellular impact of lysosomal dysfunction","volume":"199","author":"Platt","year":"2012","journal-title":"J Cell Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e2004411","DOI":"10.1371\/journal.pbio.2004411","article-title":"Role of the AP-5 adaptor protein complex in late endosome-to-Golgi retrieval","volume":"16","author":"Hirst","year":"2018","journal-title":"PLoS Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e98","DOI":"10.1212\/NXG.0000000000000098","article-title":"Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48)","volume":"2","author":"Hirst","year":"2016","journal-title":"Neurol Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"4984","DOI":"10.1093\/hmg\/ddv220","article-title":"Loss of AP-5 results in accumulation of aberrant endolysosomes: defining a new type of lysosomal storage disease","volume":"24","author":"Hirst","year":"2015","journal-title":"Hum Mol Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.nbd.2019.03.026","article-title":"A mouse model for SPG48 reveals a block of autophagic flux upon disruption of adaptor protein complex five","volume":"127","author":"Khundadze","year":"2019","journal-title":"Neurobiol Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"116620","DOI":"10.1016\/j.jns.2019.116620","article-title":"Ophthalmological changes in hereditary spastic paraplegia and other genetic diseases with spastic paraplegia","volume":"409","author":"de Freitas","year":"2020","journal-title":"J Neurol Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1002\/mds.28487","article-title":"et al. Expanding the spectrum of AP5Z1-related hereditary spastic paraplegia (HSP-SPG48): a multicenter study on a rare disease","volume":"36","author":"Breza","year":"2021","journal-title":"Mov Disord."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2517","DOI":"10.1093\/hmg\/ddy156","article-title":"Impaired mitochondrial dynamics underlie axonal defects in hereditary spastic paraplegias","volume":"27","author":"Denton","year":"2018","journal-title":"Hum Mol Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"awab488","DOI":"10.1093\/brain\/awab488","article-title":"Inhibiting mitochondrial fission rescues degeneration in hereditary spastic paraplegia neurons","volume":"145","author":"Chen","year":"2022","journal-title":"Brain"},{"key":"B15","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1093\/humupd\/dmab001","article-title":"Mitochondria: their role in spermatozoa and in male infertility","volume":"27","author":"Boguenet","year":"2021","journal-title":"Hum Reprod Update."},{"key":"B16","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.mito.2018.10.001","article-title":"A deafness-associated mitochondrial DNA mutation altered the tRNASer(UCN) metabolism and mitochondrial function","volume":"46","author":"Xue","year":"2019","journal-title":"Mitochondrion."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1093\/brain\/awu121","article-title":"Overlapping phenotypes in complex spastic paraplegias SPG11, SPG15, SPG35 and SPG48","volume":"137","author":"Pensato","year":"2014","journal-title":"Brain."},{"key":"B18","doi-asserted-by":"publisher","first-page":"981","DOI":"10.3389\/fneur.2018.00981","article-title":"Next generation molecular diagnosis of hereditary spastic paraplegias: an italian cross-sectional study","volume":"9","author":"D'Amore","year":"2018","journal-title":"Front Neurol."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1156100\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T04:29:20Z","timestamp":1680496160000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1156100\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,3]]},"references-count":18,"alternative-id":["10.3389\/fneur.2023.1156100"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2023.1156100","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,3]]},"article-number":"1156100"}}