{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T11:45:17Z","timestamp":1782819917553,"version":"3.54.5"},"reference-count":0,"publisher":"Ubiquity Press, Ltd.","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research (ICMR), New Delhi","doi-asserted-by":"crossref","award":["54\/12\/2019-HUM\/BMS"],"award-info":[{"award-number":["54\/12\/2019-HUM\/BMS"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TOHM"],"abstract":"<jats:p>Background: Autosomal recessive spastic paraplegia 35 (SPG35), also known as Fatty acid hydroxylase-associated neurodegeneration (FAHN), is a rare recessive neurodegenerative disorder with or without ataxia, dystonia, and other neurological findings. It is caused by genetic variants in FA2H, which encodes fatty acid 2-hydroxylase.\nObjective: To report the clinical, electrophysiological, radiological, and genetic profile of patients diagnosed with FAHN.\nMethods: We performed a retrospective chart review of genetically proven cases of FAHN from our database.\nResults: We identified eight patients (6 females) with genetically proven FAHN. All patients presented with first-decade onset pyramidal syndrome with or without ataxia and with radiological findings of callosal atrophy, peri-ventricular white matter hyperintensity, and cerebellar atrophy. Iron accumulation was observed in four of them. Whole exome sequencing revealed seven unique variants including three missense variants (c.83G&gt;C;p.Arg28Pro, c.130C&gt;A;p.Pro44Thr, and c.703C&gt;T;p.Arg235Cys), a stop-gain variant (c.379C&gt;T;p.Arg127Ter), a frameshift deletion variant (c.536delT;p.Leu179Argfs*62), a in-frame deletion variant (c.200_202del;p.His67del) and a in-frame duplication variant (c.86_97dup;p.Arg29_Arg32dup). The variants p.Pro44Thr, p.Arg28Pro, p.Arg29_Arg32dup, and p.His67del are located in the iron-binding region, and the p.Arg235Cys in the hydroxylase domain. The other two variants, p.Arg127Ter and p.Leu179Argfs*62, predictively cause protein truncation, leading to loss of the transmembrane domain and the fatty acid hydroxylase domain, which in turn may result in disruption of fatty acid alpha-hydroxylase activity of FA2H.\nConclusion: Our study identifies novel variants associated with FA2H in FAHN patients, highlighting their possible roles in iron binding and in the loss of the transmembrane and catalytic domains.<\/jats:p>","DOI":"10.5334\/tohm.1162","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T14:06:38Z","timestamp":1772719598000},"page":"15","source":"Crossref","is-referenced-by-count":1,"title":["Clinical, Radiological, and Genetic Profile of Patients with FA2H-Associated Neurodegeneration: Eight Cases from India and a Review of the Literature"],"prefix":"10.5334","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3634-2219","authenticated-orcid":false,"given":"Vikram V.","family":"Holla","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6550-8505","authenticated-orcid":false,"given":"Riyanka","family":"Kumari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7736-8597","authenticated-orcid":false,"given":"Neeharika","family":"Sriram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7933-8826","authenticated-orcid":false,"given":"Nitish","family":"Kamble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5218-0264","authenticated-orcid":false,"given":"Jitender","family":"Saini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8016-9089","authenticated-orcid":false,"given":"Ravi","family":"Yadav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2257-3630","authenticated-orcid":false,"given":"Babylakshmi","family":"Muthusamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4085-2377","authenticated-orcid":false,"given":"Pramod Kumar","family":"Pal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3285","published-online":{"date-parts":[[2026,3,5]]},"container-title":["Tremor and Other Hyperkinetic 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