title: SEPT9 gene sequencing analysis reveals recurrent mutations in hereditary neuralgic amyotrophy.
abstract: BACKGROUND
  Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder that manifests as recurrent, episodic, painful brachial neuropathies. A gene for HNA maps to chromosome 17q25.3 where mutations in SEPT9, encoding the septin-9 protein, have been identified.
  
  
  OBJECTIVE
  To determine the frequency and type of mutations in the SEPT9 gene in a new cohort of 42 unrelated HNA pedigrees.
  
  
  METHODS
  DNA sequencing of all exons and intron-exon boundaries for SEPT9 was carried out in an affected individual in each pedigree from our HNA cohort. Genotyping using microsatellite markers spanning the SEPT9 gene was also used to identify pedigrees with a previously reported founder haplotype.
  
  
  RESULTS
  Two missense mutations were found: c.262C>T (p.Arg88Trp) in seven HNA pedigrees and c.278C>T (p.Ser93Phe) in one HNA pedigree. Sequencing of other known exons in SEPT9 detected no additional disease-associated mutations. A founder haplotype, without defined mutations in SEPT9, was present in seven pedigrees.
  
  
  CONCLUSIONS
  We provide further evidence that mutation of the SEPT9 gene is the molecular basis of some cases of hereditary neuralgic amyotrophy (HNA). DNA sequencing of SEPT9 demonstrates a restricted set of mutations in this cohort of HNA pedigrees. Nonetheless, sequence analysis will have an important role in mutation detection in HNA. Additional techniques will be required to find SEPT9 mutations in an HNA founder haplotype and other pedigrees.
authors.affiliation: Department of Pediatrics, University of Washington School of Medicine, Seattle, 98195-6320, USA. mhanni@u.washington.edu
authors.forename: M C
authors.initials: MC
authors.lastname: Hannibal
authors.forename: E K
authors.initials: EK
authors.lastname: Ruzzo
authors.forename: L R
authors.initials: LR
authors.lastname: Miller
authors.forename: B
authors.initials: B
authors.lastname: Betz
authors.forename: J G
authors.initials: JG
authors.lastname: Buchan
authors.forename: D M
authors.initials: DM
authors.lastname: Knutzen
authors.forename: K
authors.initials: K
authors.lastname: Barnett
authors.forename: M L
authors.initials: ML
authors.lastname: Landsverk
authors.forename: A
authors.initials: A
authors.lastname: Brice
authors.forename: E
authors.initials: E
authors.lastname: LeGuern
authors.forename: H M
authors.initials: HM
authors.lastname: Bedford
authors.forename: B B
authors.initials: BB
authors.lastname: Worrall
authors.forename: S
authors.initials: S
authors.lastname: Lovitt
authors.forename: S H
authors.initials: SH
authors.lastname: Appel
authors.forename: E
authors.initials: E
authors.lastname: Andermann
authors.forename: T D
authors.initials: TD
authors.lastname: Bird
authors.forename: P F
authors.initials: PF
authors.lastname: Chance
mesh_terms: D001483:Base Sequence; D020968:Brachial Plexus Neuritis / Q000235:genetics*; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D058112:Septins; D017421:Sequence Analysis
chemical_list: D020558:GTP Phosphohydrolases; C474315:SEPTIN9 protein, human; D058112:Septins