title: Mutations, clinical findings and survival estimates in South American patients with X-linked adrenoleukodystrophy.
abstract: In this study, we analyzed the ABCD1 gene in X-linked adrenoleukodystrophy (X-ALD) patients and relatives from 38 unrelated families from South America, as well as phenotypic proportions, survival estimates, and the potential effect of geographical origin in clinical characteristics.
  
  
  METHODS
  X- ALD patients from Brazil, Argentina and Uruguay were invited to participate in molecular studies to determine their genetic status, characterize the mutations and improve the genetic counseling of their families. All samples were screened by SSCP analysis of PCR fragments, followed by automated DNA sequencing to establish the specific mutation in each family. Age at onset and at death, male phenotypes, genetic status of women, and the effect of family and of latitude of origin were also studied.
  
  
  RESULTS
  We identified thirty-six different mutations (twelve novel). This population had an important allelic heterogeneity, as only p.Arg518Gln was repeatedly found (three families). Four cases carried de novo mutations. Intra-familiar phenotype variability was observed in all families. Out of 87 affected males identified, 65% had the cerebral phenotype (CALD). The mean (95% CI) ages at onset and at death of the CALD were 10.9 (9.1-12.7) and 24.7 (19.8-29.6) years. No association was found between phenotypic manifestations and latitude of origin. One index-case was a girl with CALD who carried an ABCD1 mutation, and had completely skewed X inactivation.
  
  
  CONCLUSIONS
  This study extends the spectrum of mutations in X-ALD, confirms the high rates of de novo mutations and the absence of common mutations, and suggests a possible high frequency of cerebral forms in our population.
authors.affiliation: Gene Therapy Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Fernanda dos Santos
authors.initials: Fdos S
authors.lastname: Pereira
authors.forename: Ursula
authors.initials: U
authors.lastname: Matte
authors.forename: Clarissa Troller
authors.initials: CT
authors.lastname: Habekost
authors.forename: Raphael Machado
authors.initials: RM
authors.lastname: de Castilhos
authors.forename: Antonette Souto
authors.initials: AS
authors.lastname: El Husny
authors.forename: Charles Marques
authors.initials: CM
authors.lastname: Lourenço
authors.forename: Angela M
authors.initials: AM
authors.lastname: Vianna-Morgante
authors.forename: Liane
authors.initials: L
authors.lastname: Giuliani
authors.forename: Marcial Francis
authors.initials: MF
authors.lastname: Galera
authors.forename: Rachel
authors.initials: R
authors.lastname: Honjo
authors.forename: Chong Ae
authors.initials: CA
authors.lastname: Kim
authors.forename: Juan
authors.initials: J
authors.lastname: Politei
authors.forename: Carmen Regla
authors.initials: CR
authors.lastname: Vargas
authors.forename: Laura Bannach
authors.initials: LB
authors.lastname: Jardim
mesh_terms: D000293:Adolescent; D000326:Adrenoleukodystrophy / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality*; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D001118:Argentina; D001921:Brain / Q000473:pathology; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D014583:Uruguay