An Alu-mediated rearrangement causing a 3.2kb deletion and a novel two base pair deletion in AAAS gene as the cause of triple A syndrome.

[triple a syndrome]

Triple A syndrome is an autosomal recessive disorder resulting from deleterious mutations in the AAAS gene located on chromosome 12 q 13 . Typical clinical presentation of this syndrome includes adrenal insufficiency , achalasia , and alacrima . A 10 -year -old female was diagnosed with Triple A syndrome at the age of 1 year . Initial analysis of the AAAS gene revealed apparently homozygosity for a novel 2 bp deletion in exon 1 . The father of the patient was heterozygous for this mutation but the mother and the maternal grandparents were apparently homozygous for the wild-type . Further studies demonstrated that the patient carried an intragenic 3 .2 kb deletion within both 5 ' and 3 ' breakpoints located within Alu-repeats . The deletion includes 5 '-flanking region , exon 1 , intron 1 , exon 2 , and part of intron 2 sequences of the AAAS gene . This Alu-mediated deletion was inherited from her mother and maternal grandmother . This is the first report that Alu-mediated rearrangement in conjunction with a novel two -bp deletion of the AAAS gene is a cause of Triple A syndrome . The results of our study lead to the hypothesis that an Alu-mediated mechanism may be responsible for large alterations in the AAAS gene . We also stress the importance of studying the family in genetic recessive diseases , such as Triple A syndrome , to avoid incorrect diagnosis and to provide accurate genetic counseling .