Chromosomal fragility in patients with triple A syndrome.
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.
Reshmi-Skarja
Shalini
S
Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania 15261, USA.
Huebner
Angela
A
Handschug
Katrin
K
Finegold
David N
DN
Clark
Adrian J L
AJ
Gollin
Susanne M
SM
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
C416506:AAAS protein, human; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins; D011506:Proteins; D004247:DNA