{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:38:49Z","timestamp":1790699929262,"version":"4.1.0"},"reference-count":13,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,1,26]],"date-time":"2014-01-26T00:00:00Z","timestamp":1390694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Sciences Foundation of China","doi-asserted-by":"crossref","award":["No: 30971034"],"award-info":[{"award-number":["No: 30971034"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Sciences Foundation of China","doi-asserted-by":"crossref","award":["No: 81171068"],"award-info":[{"award-number":["No: 81171068"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Sciences Foundation of China","doi-asserted-by":"crossref","award":["No: 81100845"],"award-info":[{"award-number":["No: 81100845"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2015,1]]},"abstract":"\n Hereditary spastic paraplegias (\n HSPs<\/jats:styled-content>\n ) encompass a clinically and genetically heterogeneous group of neurodegenerative disorders. Recently, mutations in fatty acid 2\u2010hydroxylase gene (\n \n FA2H<\/jats:styled-content>\n <\/jats:italic>\n ) have been identified responsible for HSPs type 35 (\n SPG35<\/jats:styled-content>\n ). This study aims to define the contribution of\n \n FA2H<\/jats:styled-content>\n <\/jats:italic>\n to Chinese autosomal recessive\n HSP<\/jats:styled-content>\n (\n AR<\/jats:styled-content>\n \u2010\n HSP<\/jats:styled-content>\n ) patients and provide insights into the enzymatic functions of the novel mutations. Direct sequencing of\n \n FA2H<\/jats:styled-content>\n <\/jats:italic>\n was conducted in 31\n AR\u2010HSP<\/jats:styled-content>\n families and 55 sporadic cases without\n \n SPG11<\/jats:styled-content>\n <\/jats:italic>\n ,\n \n SPG15<\/jats:styled-content>\n <\/jats:italic>\n ,\n \n SPG5<\/jats:styled-content>\n <\/jats:italic>\n and\n \n SPG7<\/jats:styled-content>\n <\/jats:italic>\n gene mutations. Enzymatic activity of the mutated proteins was further examined. Three novel mutations were found in two Chinese families, including two compound heterozygous mutations (c.\n 388C<\/jats:styled-content>\n >T\/p.\n L130F<\/jats:styled-content>\n and c.506+\n 6C<\/jats:styled-content>\n >G) and one homozygous mutation (c.\n 230T<\/jats:styled-content>\n >G\/p.\n L77R<\/jats:styled-content>\n ). The c.506+\n 6C<\/jats:styled-content>\n >G splice\u2010site mutation led to the deletion of exon 3. Measurement of enzymatic functions revealed a significant reduction in the enzymatic activity of\n FA2H<\/jats:styled-content>\n associated with p.\n L130F<\/jats:styled-content>\n and p.\n L77R<\/jats:styled-content>\n . Overall, our data widens the spectrum of the mutations on\n \n FA2H<\/jats:styled-content>\n <\/jats:italic>\n , and functional analyses indicate that these mutations severely impair the enzymatic activity of\n FA2H<\/jats:styled-content>\n . Furthermore, frequency analysis shows that\n SPG35<\/jats:styled-content>\n is the second most common subtype of\n AR\u2010HSP<\/jats:styled-content>\n in China.\n <\/jats:p>","DOI":"10.1111\/cge.12336","type":"journal-article","created":{"date-parts":[[2013,12,20]],"date-time":"2013-12-20T19:51:12Z","timestamp":1387569072000},"page":"85-89","source":"Crossref","is-referenced-by-count":24,"title":["SPG35<\/scp>\n contributes to the second common subtype of\n AR\u2010HSP<\/scp>\n in China: frequency analysis and functional characterization of\n \n FA2H<\/scp>\n <\/i>\n gene mutations"],"prefix":"10.1111","volume":"87","author":[{"given":"X.","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University Changsha China"},{"name":"The State Key Laboratory of Medical Genetics Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University Changsha China"},{"name":"The State Key Laboratory of Medical Genetics Central South University Changsha China"},{"name":"The Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University Changsha China"},{"name":"The State Key Laboratory of Medical Genetics Central South University Changsha China"},{"name":"The Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Hu","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University Changsha China"},{"name":"The Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q.","family":"Pan","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Xia","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University Changsha China"},{"name":"The State Key Laboratory of Medical Genetics Central South University Changsha China"},{"name":"The Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University Changsha China"},{"name":"The State Key Laboratory of Medical Genetics Central South University Changsha China"},{"name":"The Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,1,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2012.03.025"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1299787"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20041451"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000319610.29522.8a"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.10.010"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22122"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.222"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(83)92879-9"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-6741-1_3"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1139\/y59-099"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2008.07.038"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2012.03838.x"},{"key":"e_1_2_6_14_1","article-title":"Phenotypic variability of a likely FA2H founder mutation in a family with complicated hereditary spastic paraplegia","author":"Donkervoort S","year":"2013","journal-title":"Clin Genet"}],"container-title":["Clinical 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