title: 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.
abstract: Triple A syndrome is an autosomal recessive disorder resulting from deleterious mutations in the AAAS gene located on chromosome 12q13. 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 2bp 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 3.2kb 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.
authors.affiliation: Department of Pediatrics, The University of Chicago, Chicago, IL 60637, USA. kqin@peds.bsd.uchicago.edu
authors.forename: Kenan
authors.initials: K
authors.lastname: Qin
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Du
authors.forename: Barry H
authors.initials: BH
authors.lastname: Rich
mesh_terms: D020087:Alu Elements / Q000235:genetics*; D002675:Child, Preschool; D025063:Chromosome Disorders / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D010375:Pedigree; D013577:Syndrome
chemical_list: C416506:AAAS protein, human; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins