title: Chromosomal fragility in patients with triple A syndrome.
abstract: Triple A syndrome is a rare, autosomal recessive disorder characterized by alacrima, achalasia, and adrenal insufficiency. Previous studies have shown that the triple A gene (AAAS) maps to chromosomal band 12q13. Mutations in the AAAS gene have been identified in triple A syndrome patients; however, the function of this gene is still obscure. We used classical and high-resolution chromosome analyses along with chromosome painting and DNA sequencing to study patients with triple A syndrome. We observed abnormalities in the heterochromatic region of chromosome 9 that included chromatid breaks, chromosome breaks, whole chromosome arm loss, and marker chromosomes, which occurred at unusually high frequencies in affected patients and heterozygotes. Our study raises the possibility of an association between chromosomal fragility in band 9q12 and triple A syndrome. Further investigation is necessary to understand the biologic basis of this finding in the context of triple A syndrome.
authors.affiliation: Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Shalini
authors.initials: S
authors.lastname: Reshmi-Skarja
authors.forename: Angela
authors.initials: A
authors.lastname: Huebner
authors.forename: Katrin
authors.initials: K
authors.lastname: Handschug
authors.forename: David N
authors.initials: DN
authors.lastname: Finegold
authors.forename: Adrian J L
authors.initials: AJ
authors.lastname: Clark
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Gollin
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000309:Adrenal Insufficiency / Q000473:pathology*; D000328:Adult; D000368:Aged; D002648:Child; D002872:Chromosome Deletion; D002873:Chromosome Fragility; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004931:Esophageal Achalasia / Q000473:pathology*; D005260:Female; D006801:Humans; D007765:Lacrimal Apparatus / Q000002:abnormalities*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins; D011506:Proteins / Q000235:genetics; D013577:Syndrome
chemical_list: C416506:AAAS protein, human; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins; D011506:Proteins; D004247:DNA