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.