Analysis of the AAAS gene in a Japanese patient with triple A syndrome

Triple A syndrome, also known as Allgrove syndrome, is a rare autosomal recessive disorder characterized by adrenal insufficiency, achalasia and alacrima. It has recently been reported that this syndrome is caused by mutations in the AAAS gene. In the present study, we analyzed the AAAS gene in a Japanese patient with triple A syndrome. The patient was a Japanese girl previously reported by Hirose et al. (J Jpn Pediatr Soc 102: 912-915, 1998). The parents of the patient were first cousins. The patient was confirmed to have alacrima and isolated glucocorticoid deficiency at the age of 2 years. She later developed achalasia of the cardia, and was diagnosed as having triple A syndrome. The AAAS gene was amplified by the PCR method, and the PCR products were directly sequenced. The patient was homozygous for a novel nonsense mutation Q237X, changing codon 237 encoding Gln (CAA) to a stop codon (TAA). The parents were heterozygous for the Q237X mutation. The AAAS gene encodes a protein of 546 amino acids, ALADIN. The Q237X mutation is predicted to result in a truncated and presumably non-functioning ALADIN protein, thus causing the clinically manifest syndrome in the patient. To our knowledge, this is the first report on AAAS gene mutations in Japan.