title: Clinical and Molecular Characterization of BSCL2 Mutations in a Taiwanese Cohort with Hereditary Neuropathy.
abstract: BACKGROUND
  A small group of patients with inherited neuropathy that has been shown to be caused by mutations in the BSCL2 gene. However, little information is available about the role of BSCL2 mutations in inherited neuropathies in Taiwan.
  
  
  RESULTS
  Utilizing targeted sequencing, 76 patients with molecularly unassigned Charcot-Marie-Tooth disease type 2 (CMT2) and 8 with distal hereditary motor neuropathy (dHMN), who were selected from 348 unrelated patients with inherited neuropathies, were screened for mutations in the coding regions of BSCL2. Two heterozygous BSCL2 mutations, p.S90L and p.R96H, were identified, of which the p.R96H mutation is novel. The p.S90L was identified in a pedigree with CMT2 while the p.R96H was identified in a patient with apparently sporadic dHMN. In vitro studies demonstrated that the p.R96H mutation results in a remarkably low seipin expression and reduced cell viability.
  
  
  CONCLUSIONS
  BSCL2 mutations account for a small number of patients with inherited neuropathies in Taiwan. The p.R96H mutation is associated with dHMN. This study expands the molecular spectrum of BSCL2 mutations and also emphasizes the pathogenic role of BSCL2 mutations in molecularly unassigned hereditary neuropathies.
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.|Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.
authors.forename: Cheng-Tsung
authors.initials: CT
authors.lastname: Hsiao
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.|Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.|Brain Research Center, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Pei-Chien
authors.initials: PC
authors.lastname: Tsai
authors.affiliation: Department of Neurology, School of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan, ROC.
authors.forename: Chou-Ching
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.|Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.
authors.forename: Yo-Tsen
authors.initials: YT
authors.lastname: Liu
authors.affiliation: Institute of Biomedical Informatics, National Yang-Ming University School of Medicine, Taipei, Taiwan.|Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yen-Hua
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.|Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.
authors.forename: Yi-Chu
authors.initials: YC
authors.lastname: Liao
authors.affiliation: Department of Neurology, School of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan, ROC.
authors.forename: Han-Wei
authors.initials: HW
authors.lastname: Huang
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.|Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.
authors.forename: Kon-Ping
authors.initials: KP
authors.lastname: Lin
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.|Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.|Brain Research Center, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Bing-Wen
authors.initials: BW
authors.lastname: Soong
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.|Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.|Brain Research Center, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Yi-Chung
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002607:Charcot-Marie-Tooth Disease / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D044388:GTP-Binding Protein gamma Subunits / Q000737:chemistry / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009134:Muscular Atrophy, Spinal / Q000453:epidemiology / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D017354:Point Mutation; D016415:Sequence Alignment; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult
chemical_list: C432679:BSCL2 protein, human; D044388:GTP-Binding Protein gamma Subunits
references.citation: J Lipid Res. 2011 Dec;52(12):2136-2147
references.pmid: 21957196
references.citation: FEBS Lett. 2006 Apr 17;580(9):2281-4
references.pmid: 16574104
references.citation: Mol Cell Biol. 2012 Mar;32(6):1099-111
references.pmid: 22269949
references.citation: J Neurol. 2010 Oct;257(10):1661-8
references.pmid: 20461396
references.citation: Nat Genet. 2004 Mar;36(3):271-6
references.pmid: 14981520
references.citation: Neuromuscul Disord. 1998 Aug;8(6):426-31
references.pmid: 9713862
references.citation: Diabetologia. 2013 Nov;56(11):2498-506
references.pmid: 23989774
references.citation: PLoS One. 2015 Aug 05;10(8):e0133423
references.pmid: 26244500
references.citation: Nat Protoc. 2009;4(7):1073-81
references.pmid: 19561590
references.citation: Neurobiol Dis. 2002 Oct;11(1):43-52
references.pmid: 12460545
references.citation: Neurology. 2014 Sep 2;83(10):903-12
references.pmid: 25098539
references.citation: Brain. 2004 Sep;127(Pt 9):2124-30
references.pmid: 15242882
references.citation: Nat Genet. 2001 Aug;28(4):365-70
references.pmid: 11479539
references.citation: Nucleic Acids Res. 2014 Jan;42(Database issue):D191-8
references.pmid: 24253303
references.citation: Ann Neurol. 2005 Mar;57(3):415-24
references.pmid: 15732094
references.citation: J Neurochem. 2013 Feb;124(4):478-89
references.pmid: 23173741
references.citation: J Neurol Neurosurg Psychiatry. 2014 Nov;85(11):1265-72
references.pmid: 24604904
references.citation: Mol Genet Genomic Med. 2015 Mar;3(2):143-54
references.pmid: 25802885
references.citation: Biochem J. 2013 May 15;452(1):37-44
references.pmid: 23458123
references.citation: J Med Genet. 2013 Jun;50(6):401-9
references.pmid: 23564749
references.citation: Nat Methods. 2014 Apr;11(4):361-2
references.pmid: 24681721
references.citation: J Neurol Neurosurg Psychiatry. 2012 Jul;83(7):706-10
references.pmid: 22577229
references.citation: Ann Neurol. 2007 Mar;61(3):237-50
references.pmid: 17387721
references.citation: Nat Methods. 2010 Apr;7(4):248-9
references.pmid: 20354512
references.citation: Neurogenetics. 2013 Feb;14(1):35-42
references.pmid: 23142943
references.citation: J Neurochem. 2014 Apr;129(2):328-38
references.pmid: 24345054
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20890-5
references.pmid: 18093937
references.citation: Hum Mol Genet. 2014 Jan 15;23(2):502-13
references.pmid: 24026679
references.citation: Brain. 2009 Jan;132(Pt 1):8-15
references.pmid: 18790819
references.citation: PLoS One. 2011;6(12):e29393
references.pmid: 22206013
references.citation: J Neurol Neurosurg Psychiatry. 2015 Aug;86(8):873-8
references.pmid: 25430934