title: Genotypic heterogeneity and clinical phenotype in triple A syndrome: a review of the NIH experience 2000-2005.
abstract: Triple A syndrome (AAAS, OMIM#231550) is an autosomal recessive condition characterized by adrenal insufficiency, achalasia, alacrima, neurodegeneration and autonomic dysfunction. Mutations in the AAAS gene on chromosome 12q13 have been reported in several subjects with AAAS. Over the last 5 years, we have evaluated six subjects with the clinical diagnosis of AAAS. Three subjects had mutations in the AAAS gene-- including one novel mutation (IVS8+1 G>A)-- and a broad spectrum of clinical presentations. However, three subjects with classic AAAS did not have mutations in the AAAS gene on both alleles. This finding supports the notion of genetic heterogeneity for this disorder, although other genetic mechanisms cannot be excluded.
authors.affiliation: Office of the Scientific Director, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: B P
authors.initials: BP
authors.lastname: Brooks
authors.forename: R
authors.initials: R
authors.lastname: Kleta
authors.forename: C
authors.initials: C
authors.lastname: Stuart
authors.forename: M
authors.initials: M
authors.lastname: Tuchman
authors.forename: A
authors.initials: A
authors.lastname: Jeong
authors.forename: S G
authors.initials: SG
authors.lastname: Stergiopoulos
authors.forename: T
authors.initials: T
authors.lastname: Bei
authors.forename: B
authors.initials: B
authors.lastname: Bjornson
authors.forename: L
authors.initials: L
authors.lastname: Russell
authors.forename: J-P
authors.initials: JP
authors.lastname: Chanoine
authors.forename: S
authors.initials: S
authors.lastname: Tsagarakis
authors.forename: Lr
authors.initials: L
authors.lastname: Kalsner
authors.forename: Ca
authors.initials: C
authors.lastname: Stratakis
mesh_terms: D000293:Adolescent; D000309:Adrenal Insufficiency / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12; D002882:Chromosomes, Human, Pair 13; D004931:Esophageal Achalasia / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D018740:Genetic Heterogeneity; D006801:Humans; D007766:Lacrimal Apparatus Diseases / Q000235:genetics*; D008297:Male; D009154:Mutation; D009316:National Institutes of Health (U.S.); D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins; D010641:Phenotype; D011506:Proteins; D013577:Syndrome; D014481:United States
chemical_list: C416506:AAAS protein, human; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins; D011506:Proteins