title: Segmental copy number loss of SFMBT1 gene in elderly individuals with ventriculomegaly: a community-based study.
abstract: OBJECTIVE
  Idiopathic normal pressure hydrocephalus (iNPH) is clinically important as a treatable gait disturbance or preventable dementia by shunt operation. We have recently reported that approximately 1.5% of the elderly living in a Japanese community showed ventriculomegaly with features of iNPH on MRI (VIM), which may represent a preclinical stage of iNPH. The purpose of the present study was to identify a possible genetic change in VIM subjects.
  
  
  METHODS
  Eight subjects with VIM and 10 healthy individuals were examined for copy number variations (CNV) with a CNV-targeted whole-genome oligonucleotide microarray (Agilent 400 K CNV array). Another panel of 100 healthy Japanese individuals was screened for CNV by whole-genome using the deCODE-Illumina CNV 370 K chip. Immunohistochemical examination of the human brain was performed using an avidin-biotin-peroxidase complex method.
  
  
  RESULTS
  Among several genetic changes observed, a copy number loss within the SFMBT1 gene was seen in half of the VIM cases (4 of 8 cases), that was rare among the Japanese control subjects (0/10 by Agilent 400 K CNV array or 1/100 by deCODE/Illumina CNV 370 K chip). Immunohistochemical examination of the human brain revealed that the SFMBT1 protein was localized mainly in the arterial walls, the ependymal cells, and the epithelium of the choroid plexus, all of which play a crucial role in the CSF circulation.
  
  
  CONCLUSIONS
  A segmental copy number loss of the SFMBT1 gene may be involved in the pathological process in some individuals with VIM/iNPH.
authors.affiliation: Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Yamagata University Faculty of Medicine, Japan. tkato@med.id.yamagata-u.ac.jp
authors.forename: Takeo
authors.initials: T
authors.lastname: Kato
authors.forename: Hidenori
authors.initials: H
authors.lastname: Sato
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Emi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Seino
authors.forename: Shigeki
authors.initials: S
authors.lastname: Arawaka
authors.forename: Chifumi
authors.initials: C
authors.lastname: Iseki
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Manabu
authors.initials: M
authors.lastname: Wada
authors.forename: Toru
authors.initials: T
authors.lastname: Kawanami
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D006849:Hydrocephalus / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006850:Hydrocephalus, Normal Pressure / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007564:Japan; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D012097:Repressor Proteins; C523369:SFMBT1 protein, human