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

Item Type:Article
Title:Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene
Creators Name:Handschug, K. and Sperling, S. and Yoon, S.J. and Hennig, S. and Clark, A.J. and Huebner, A.
Abstract: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.
Keywords:Adrenal Insufficiency, Amino Acid Sequence, Base Sequence, DNA, DNA Mutational Analysis, Esophageal Achalasia, Family Health, Genetic Predisposition to Disease, Lacrimal Apparatus, Microsatellite Repeats, Molecular Sequence Data, Multiple Abnormalities, Mutation, Nucleic Acid Repetitive Sequences, Pair 12 Human Chromosomes, Pedigree, Single-Stranded Conformational Polymorphism, Syndrome
Source:Human Molecular Genetics
ISSN:0964-6906
Publisher:Oxford University Press (U.K.)
Volume:10
Number:3
Page Range:283-290
Date:1 February 2001
Official Publication:https://doi.org/10.1093/hmg/10.3.283
PubMed:View item in PubMed

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