The triple A syndrome (MIM*231550) is a rare autosomal recessive disorder 
characterized by adrenocorticotropic hormone (ACTH) resistant adrenal failure, 
achalasia, alacrima and a variety of neurological and dermatological features. 
Adrenal insufficiency usually presents in the first decade of life, however in 
some patients it may occur later in life or may even lack completely. Recently, 
we and others identified a novel gene on chromosome 12q13, designated AAAS 
(Achalasia-Addisonianism-Alacrima-Syndrome gene) which is mutated in patients 
with triple A syndrome. We investigated n=84 families including 111 patients 
with clinically suggested triple A syndrome and identified homozygous or 
compound heterozygous AAAS mutations in 78 families. Genotype/phenotype analyses 
revealed a highly variable occurrence, age of onset and severity of all clinical 
symptoms between patients with the same AAAS mutation. The obvious lack of a 
genotype/phenotype relationship is suggestive of modifying genes/factors which 
need to be determined. The AAAS protein function is unknown. With four WD 
repeats it belongs to the family of WD repeat-containing proteins which may 
exhibit a high degree of functional diversity. The subcellular localization of 
the protein and the determination of its putative binding partners will shed 
light on the role of the AAAS protein for the development and function of the 
adrenal gland and other neuroendocrine structures.