title: Multiplex families with multiple system atrophy.
abstract: BACKGROUND
  Multiple system atrophy (MSA) has been considered a sporadic disease, without patterns of inheritance.
  
  
  OBJECTIVE
  To describe the clinical features of 4 multiplex families with MSA, including clinical genetic aspects.
  
  
  METHODS
  Clinical and genetic study.
  
  
  METHODS
  Four departments of neurology in Japan. Patients Eight patients in 4 families with parkinsonism, cerebellar ataxia, and autonomic failure with age at onset ranging from 58 to 72 years. Two siblings in each family were affected with these conditions.
  
  
  METHODS
  Clinical evaluation was performed according to criteria by Gilman et al. Trinucleotide repeat expansion in the responsible genes for the spinocerebellar ataxia (SCA) series and for dentatorubral-pallidoluysian atrophy (DRPLA) was evaluated by polymerase chain reaction. Direct sequence analysis of coding regions in the alpha-synuclein gene was performed.
  
  
  RESULTS
  Consanguineous marriage was observed in 1 of 4 families. Among 8 patients, 1 had definite MSA, 5 had probable MSA, and 2 had possible MSA. The most frequent phenotype was MSA with predominant parkinsonism, observed in 5 patients. Six patients showed pontine atrophy with cross sign or slitlike signal change at the posterolateral putaminal margin or both on brain magnetic resonance imaging. Possibilities of hereditary ataxias, including SCA1 (ataxin 1, ATXN1), SCA2 (ATXN2), Machado-Joseph disease/SCA3 (ATXN1), SCA6 (ATXN1), SCA7 (ATXN7), SCA12 (protein phosphatase 2, regulatory subunit B, beta isoform; PP2R2B), SCA17 (TATA box binding protein, TBP) and DRPLA (atrophin 1; ATN1), were excluded, and no mutations in the alpha-synuclein gene were found.
  
  
  CONCLUSIONS
  Findings in these multiplex families suggest the presence of familial MSA with autosomal recessive inheritance and a genetic predisposition to MSA. Molecular genetic approaches focusing on familial MSA are expected to provide clues to the pathogenesis of MSA.
authors.affiliation: Departments of Neurology, Center for Bioresource-Based Researches, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Kenju
authors.initials: K
authors.lastname: Hara
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Momose
authors.forename: Susumu
authors.initials: S
authors.lastname: Tokiguchi
authors.forename: Mitsuteru
authors.initials: M
authors.lastname: Shimohata
authors.forename: Kenshi
authors.initials: K
authors.lastname: Terajima
authors.forename: Osamu
authors.initials: O
authors.lastname: Onodera
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Yamada
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Hirasawa
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Mizuno
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Ogata
authors.forename: Jun
authors.initials: J
authors.lastname: Goto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kanazawa
authors.forename: Masatoyo
authors.initials: M
authors.lastname: Nishizawa
authors.forename: Shoji
authors.initials: S
authors.lastname: Tsuji
mesh_terms: D000368:Aged; D001921:Brain / Q000473:pathology; D003241:Consanguinity; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000235:genetics* / Q000473:pathology*; D010375:Pedigree; D017422:Sequence Analysis, DNA; D019680:Trinucleotide Repeat Expansion; D051844:alpha-Synuclein / Q000235:genetics
chemical_list: D051844:alpha-Synuclein