Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene
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.
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Triple A syndrome is caused by autosomal recessive mutations in AAAS, which encodes a WD-repeat protein termed ALADIN.
“Triple A syndrome is caused by autosomal recessive mutations in AAAS, which encodes a WD-repeat protein termed ALADIN (630,631).”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [631]
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The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders
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- Authors
- Handschug, K.
- Affiliations
- Technische Universität Dresden (DE)
- Corresponding author
- Handschug, K.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-02-01
- Volume
- 10
- Issue
- 3
- Pages
- 283-290
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2138449464
- Cited by
- 257
- References
- 30
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 5 · 2023: 15 · 2022: 9 · 2021: 18 · 2020: 9 · 2019: 8 · 2018: 10 · 2017: 12 · 2016: 10 · 2015: 13 · 2014: 6 · 2013: 9 · 2012: 8
- FWCI
- 7.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- triple A syndrome, AAAS gene, WD-repeat proteins, autosomal recessive disorder, adrenal insufficiency, achalasia, alacrima, chromosome 12q13, gene mapping, homozygous mutation, compound heterozygosity, loss-of-function mutations, gene identification
- MeSH terms
- Abnormalities, Multiple, Adrenal Insufficiency, Amino Acid Sequence, Base Sequence, Chromosomes, Human, Pair 12, DNA, DNA Mutational Analysis, Esophageal Achalasia, Family Health, Female, Humans, Lacrimal Apparatus, Male, Molecular Sequence Data, Mutation, Pedigree, Repetitive Sequences, Nucleic Acid, Syndrome, Polymorphism, Single-Stranded Conformational, Microsatellite Repeats, Genetic Predisposition to Disease
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