Journal Article

Triple A syndrome is caused by mutations in <i>AAAS</i>, a new WD-repeat protein gene

Katrin Handschug, Silke Sperling, Sung-Joo Kim Yoon, Steffen Hennig, Adrian J.L. Clark and Angela Huebner

in Human Molecular Genetics

Volume 10, issue 3, pages 283-290
Published in print February 2001 | ISSN: 0964-6906
Published online February 2001 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/10.3.283
Triple A syndrome is caused by mutations in AAAS,  a new WD-repeat protein gene

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The triple A syndrome (MIM 231550) is a rare autosomal recessive disorder characterized by adrenal insufficiency, achalasia and alacrima. The frequent association with a variety of neurological features may result in a severely disabling disease. We previously mapped the syndrome to a 6 cM interval on chromosome 12q13 and have now refined the critical region to 0 cM between KRT8 and D12S1651. Overlapping bacterial artificial chromosome (BAC) sequences of a high resolution BAC/P1-derived artificial chromosome (PAC) contig were screened for gene content and a novel gene encoding a 546 amino acid polypeptide was identified. In nine triple A syndrome patients eight different homozygous and compound heterozygous mutations were found in this gene, most of them leading to a truncated protein suggesting loss of function. RNA blotting experiments revealed marked expression in neuroendocrine and gastrointestinal structures, which are predominantly affected in triple A syndrome, supporting the hypothesis that mutations in this triple A syndrome gene (AAAS) are responsible for the disease. The predicted protein belongs to the family of WD repeat-containing proteins which exhibit a high degree of functional diversity including regulation of signal transduction, RNA processing and transcription.

Journal Article.  4525 words.  Illustrated.

Subjects: Genetics and Genomics

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