{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:58:08Z","timestamp":1791496688448,"version":"4.3.4"},"reference-count":42,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T00:00:00Z","timestamp":1664236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the excellent personnel training plan for Shanghai Health and Family System","award":["2018YQ13"],"award-info":[{"award-number":["2018YQ13"]}]},{"name":"the excellent personnel training plan for Shanghai Health and Family System","award":["ynlc201907"],"award-info":[{"award-number":["ynlc201907"]}]},{"name":"the excellent personnel training plan for Shanghai Health and Family System","award":["81870889"],"award-info":[{"award-number":["81870889"]}]},{"name":"the excellent personnel training plan for Shanghai Health and Family System","award":["82071258"],"award-info":[{"award-number":["82071258"]}]},{"name":"Hospital-level Project of Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital","award":["2018YQ13"],"award-info":[{"award-number":["2018YQ13"]}]},{"name":"Hospital-level Project of Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital","award":["ynlc201907"],"award-info":[{"award-number":["ynlc201907"]}]},{"name":"Hospital-level Project of Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital","award":["81870889"],"award-info":[{"award-number":["81870889"]}]},{"name":"Hospital-level Project of Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital","award":["82071258"],"award-info":[{"award-number":["82071258"]}]},{"name":"National Natural Science Foundation of China","award":["2018YQ13"],"award-info":[{"award-number":["2018YQ13"]}]},{"name":"National Natural Science Foundation of China","award":["ynlc201907"],"award-info":[{"award-number":["ynlc201907"]}]},{"name":"National Natural Science Foundation of China","award":["81870889"],"award-info":[{"award-number":["81870889"]}]},{"name":"National Natural Science Foundation of China","award":["82071258"],"award-info":[{"award-number":["82071258"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Mutations in HSPB1 are known to cause Charcot-Marie-Tooth disease type 2F (CMT2F) and distal hereditary motor neuropathy (dHMN). In this study, we presented three patients with mutation in HSPB1 who were diagnosed with dHMN. Proband 1 was a 14-year-old male with progressive bilateral lower limb weakness and walking difficulty for four years. Proband 2 was a 65-year-old male with chronic lower limb weakness and restless legs syndrome from the age of 51. Proband 3 was a 50-year-old female with progressive weakness, lower limbs atrophy from the age of 44. The nerve conduction studies (NCS) suggested axonal degeneration of the peripheral motor nerves and needle electromyography (EMG) revealed chronic neurogenic changes in probands. Open sural nerve biopsy for proband 2 and the mother of proband 1 showed mild to moderate loss of myelinated nerve fibers with some nerve fiber regeneration. A novel p.V97L in HSPB1 was identified in proband 3, the other two variants (p.P182A and p.R127W) in HSPB1 have been reported previously. The functional studies showed that expressing mutant p.V97L HSPB1 in SH-SY5Y cells displayed a decreased cell activity and increased apoptosis under stress condition. Our study expands the clinical phenotypic spectrum and etiological spectrum of HSPB1 mutation.<\/jats:p>","DOI":"10.3390\/biom12101382","type":"journal-article","created":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T21:23:27Z","timestamp":1664313807000},"page":"1382","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Heterogeneous Clinical Phenotypes of dHMN Caused by Mutation in HSPB1 Gene: A Case Series"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0533-212X","authenticated-orcid":false,"given":"Xiya","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, 600 Yishan Road, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2931-0275","authenticated-orcid":false,"given":"Jiawei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, 600 Yishan Road, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feixia","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, 600 Yishan Road, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wotu","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, 600 Yishan Road, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, 600 Yishan Road, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghua","family":"Luan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, 600 Yishan Road, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, 600 Yishan Road, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1742-9877","authenticated-orcid":false,"given":"Li","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, 600 Yishan Road, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/sj.ejhg.5200686","article-title":"A new locus for autosomal dominant Charcot-Marie-Tooth disease type 2 (CMT2F) maps to chromosome 7q11-q21","volume":"9","author":"Ismailov","year":"2001","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1038\/ng1354","article-title":"Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy","volume":"36","author":"Evgrafov","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"116809","DOI":"10.1016\/j.jns.2020.116809","article-title":"Mutations in heat shock protein beta-1 (HSPB1) are associated with a range of clinical phenotypes related to different patterns of motor neuron dysfunction: A case series","volume":"413","author":"Katz","year":"2020","journal-title":"J. Neurol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1212\/01.wnl.0000319696.14225.67","article-title":"Mutations in the HSP27 (HSPB1) gene cause dominant, recessive, and sporadic distal HMN\/CMT type 2","volume":"71","author":"Houlden","year":"2008","journal-title":"Neurology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1002\/acn3.51364","article-title":"Charcot-Marie-Tooth disease type 2F associated with biallelic HSPB1 mutations","volume":"8","author":"Abati","year":"2021","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1002\/acn3.51362","article-title":"Early and late manifestations of neuropathy due to HSPB1 mutation in the Jewish Iranian population","volume":"8","author":"Greenbaum","year":"2021","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e774","DOI":"10.1002\/brb3.774","article-title":"A novel p.T139M mutation in HSPB1 highlighting the phenotypic spectrum in a family","volume":"7","author":"Amornvit","year":"2017","journal-title":"Brain Behav."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1136\/jnnp.2009.181636","article-title":"Heat shock protein 27 R127W mutation: Evidence of a continuum between axonal Charcot-Marie-Tooth and distal hereditary motor neuropathy","volume":"81","author":"Solla","year":"2010","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1002\/humu.23062","article-title":"Molecular Chaperones in the Pathogenesis of Amyotrophic Lateral Sclerosis: The Role of HSPB1","volume":"37","author":"Capponi","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_10","first-page":"75","article-title":"Rare variants of HSPB1 are probably associated with amyotrophic lateral sclerosis","volume":"41","author":"Chen","year":"2021","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1111\/jns.12139","article-title":"A novel heat shock protein 27 homozygous mutation: Widening of the continuum between MND\/dHMN\/CMT2","volume":"20","author":"Scarlato","year":"2015","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1111\/ene.14700","article-title":"Distal hereditary motor neuropathies: Mutation spectrum and genotype-phenotype correlation","volume":"28","author":"Frasquet","year":"2021","journal-title":"Eur. J. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/j.1529-8027.2011.00361.x","article-title":"HSPB1 and HSPB8 in inherited neuropathies: Study of an Italian cohort of dHMN and CMT2 patients","volume":"16","author":"Capponi","year":"2011","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1111\/ene.14260","article-title":"Molecular analysis and clinical diversity of distal hereditary motor neuropathy","volume":"27","author":"Liu","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1111\/jcmm.17239","article-title":"Genetic analysis of potential biomarkers and therapeutic targets in ferroptosis from coronary artery disease","volume":"26","author":"Wu","year":"2022","journal-title":"J. Cell Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"112225","DOI":"10.1016\/j.biopha.2021.112225","article-title":"HSPB1 inhibitor J2 attenuates lung inflammation through direct modulation of Ym1 production and paracrine signaling","volume":"143","author":"Oh","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"140680","DOI":"10.1016\/j.bbapap.2021.140680","article-title":"HSPB1 influences mitochondrial respiration in ER-stressed beta cells","volume":"1869","author":"Mule","year":"2021","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1016\/j.hrthm.2021.06.1194","article-title":"Atrial heat shock protein levels are associated with early postoperative and persistence of atrial fibrillation","volume":"18","author":"Ramos","year":"2021","journal-title":"Heart Rhythm"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/jcb.28266","article-title":"HSPB1 rs2070804 polymorphism is associated with the depth of primary tumor","volume":"121","author":"Hung","year":"2020","journal-title":"J. Cell Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5107","DOI":"10.1007\/s11033-022-07222-6","article-title":"The protective role of HSP27 in ocular diseases","volume":"49","author":"Sooraj","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1007\/s00018-005-5190-4","article-title":"Small heat shock proteins: Molecular structure and chaperone function","volume":"62","author":"Sun","year":"2005","journal-title":"Cell Mol. Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"842149","DOI":"10.3389\/fmolb.2022.842149","article-title":"Insights on Human Small Heat Shock Proteins and Their Alterations in Diseases","volume":"9","author":"Tedesco","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7718","DOI":"10.1016\/S0021-9258(18)42574-4","article-title":"Copurification of small heat shock protein with alpha B crystallin from human skeletal muscle","volume":"267","author":"Kato","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00401-013-1133-6","article-title":"Charcot-Marie-Tooth causing HSPB1 mutations increase Cdk5-mediated phosphorylation of neurofilaments","volume":"126","author":"Holmgren","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0896-6273(02)00941-8","article-title":"Hsp27 upregulation and phosphorylation is required for injured sensory and motor neuron survival","volume":"36","author":"Benn","year":"2002","journal-title":"Neuron"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1093\/hmg\/ddx216","article-title":"Mitochondrial deficits and abnormal mitochondrial retrograde axonal transport play a role in the pathogenesis of mutant Hsp27-induced Charcot Marie Tooth Disease","volume":"26","author":"Kalmar","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1093\/hmg\/11.9.1137","article-title":"Heat shock protein 27 prevents cellular polyglutamine toxicity and suppresses the increase of reactive oxygen species caused by huntingtin","volume":"11","author":"Wyttenbach","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1080\/15548627.2019.1569930","article-title":"Neuropathy-causing mutations in HSPB1 impair autophagy by disturbing the formation of SQSTM1\/p62 bodies","volume":"15","author":"Haidar","year":"2019","journal-title":"Autophagy"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/35023595","article-title":"Hsp27 negatively regulates cell death by interacting with cytochrome c","volume":"2","author":"Bruey","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.nmd.2016.10.001","article-title":"Pilot phenotype and natural history study of hereditary neuropathies caused by mutations in the HSPB1 gene","volume":"27","author":"Rossor","year":"2017","journal-title":"Neuromuscul. Disord."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s10038-005-0280-6","article-title":"Small heat shock protein 27 mutation in a Japanese patient with distal hereditary motor neuropathy","volume":"50","author":"Kijima","year":"2005","journal-title":"J. Hum. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1016\/j.biocel.2012.04.002","article-title":"Small heat shock proteins HSP27 (HspB1), \u03b1B-crystallin (HspB5) and HSP22 (HspB8) as regulators of cell death","volume":"44","author":"Acunzo","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/jns.12252","article-title":"Clinical and genetic features of Charcot-Marie-Tooth disease 2F and hereditary motor neuropathy 2B in Japan","volume":"23","author":"Tanabe","year":"2018","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e103811","DOI":"10.15252\/embj.2019103811","article-title":"A weakened interface in the P182L variant of HSP27 associated with severe Charcot-Marie-Tooth neuropathy causes aberrant binding to interacting proteins","volume":"40","author":"Alderson","year":"2021","journal-title":"EMBO J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1016\/j.bbapap.2014.09.005","article-title":"Characterization of human small heat shock protein HspB1 that carries C-terminal domain mutations associated with hereditary motor neuron diseases","volume":"1844","author":"Chalova","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA)-Proteins Proteom."},{"key":"ref_36","first-page":"510","article-title":"Mutation analysis of small heat shock protein 27 gene in Chinese patients with Charcot-Marie-Tooth disease","volume":"22","author":"Liu","year":"2005","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.bbacli.2015.03.002","article-title":"Truncated HSPB1 causes axonal neuropathy and impairs tolerance to unfolded protein stress","volume":"3","author":"Ylikallio","year":"2015","journal-title":"BBA Clin."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/jns.12165","article-title":"Late onset dHMN II caused by c.404C>G mutation in HSPB1 gene","volume":"21","author":"Oberstadt","year":"2016","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1001\/archneur.62.8.1201","article-title":"Mutation analysis of the small heat shock protein 27 gene in chinese patients with Charcot-Marie-Tooth disease","volume":"62","author":"Tang","year":"2005","journal-title":"Arch. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.abb.2013.07.028","article-title":"Structure and properties of G84R and L99M mutants of human small heat shock protein HspB1 correlating with motor neuropathy","volume":"538","author":"Nefedova","year":"2013","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.bbrc.2012.11.051","article-title":"Mutants of human \u03b1B-crystallin cause enhanced protein aggregation and apoptosis in mammalian cells: Influence of co-expression of HspB1","volume":"430","author":"Raju","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1046\/j.1471-4159.2003.02273.x","article-title":"HSP27 but not HSP70 has a potent protective effect against alpha-synuclein-induced cell death in mammalian neuronal cells","volume":"88","author":"Zourlidou","year":"2004","journal-title":"J. Neurochem."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/10\/1382\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:40:19Z","timestamp":1760143219000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/10\/1382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,27]]},"references-count":42,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["biom12101382"],"URL":"https:\/\/doi.org\/10.3390\/biom12101382","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,27]]}}}