Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (64)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Handschug, K.
Right arrow Articles by Huebner, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Handschug, K.
Right arrow Articles by Huebner, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2001, Vol. 10, No. 3 283-290
© 2001 Oxford University Press

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

Katrin Handschug1, Silke Sperling2, Sung-Joo Kim Yoon3, Steffen Hennig2, Adrian J.L. Clark4 and Angela Huebner1,+

1Children’s Hospital, Technical University Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany, 2Max-Planck-Institute of Molecular Genetics, D-14195 Berlin, Germany, 3Research Institute of Molecular Genetics, Catholic Research Institutes of Medical Sciences, Seoul 137-701, Korea and 4Departments of Endocrinology, St Bartholomew’s and the Royal London School of Medicine and Dentistry, London EC1A 7BE, UK

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.

+ To whom correspondence should be addressed. Tel: +49 351 458 2926; Fax: +49 351 458 4334; Email: angela.huebner@mailbox.tu-dresden.de


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Eur J EndocrinolHome page
C. V. A. Collares, J. Antunes-Rodrigues, A. C. Moreira, S. N. Franca, L. A. Pereira, M. M. S. Soares, J. Elias Junior, A. J Clark, M. de Castro, and L. L. K. Elias
Heterogeneity in the molecular basis of ACTH resistance syndrome.
Eur. J. Endocrinol., July 1, 2008; 159(1): 61 - 68.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
J. L. V. Broers, F. C. S. Ramaekers, G. Bonne, R. B. Yaou, and C. J. Hutchison
Nuclear lamins: laminopathies and their role in premature ageing.
Physiol Rev, July 1, 2006; 86(3): 967 - 1008.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
A. Huebner, P. Mann, E. Rohde, A. M. Kaindl, M. Witt, P. Verkade, S. Jakubiczka, M. Menschikowski, G. Stoltenburg-Didinger, and K. Koehler
Mice Lacking the Nuclear Pore Complex Protein ALADIN Show Female Infertility but Fail To Develop a Phenotype Resembling Human Triple A Syndrome.
Mol. Cell. Biol., March 1, 2006; 26(5): 1879 - 1887.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. Perry, O. Kecha, J. Paquette, C. Huot, G. Van Vliet, and C. Deal
Primary Adrenal Insufficiency in Children: Twenty Years Experience at the Sainte-Justine Hospital, Montreal
J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3243 - 3250.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. M. Cronshaw and M. J. Matunis
The nuclear pore complex protein ALADIN is mislocalized in triple A syndrome
PNAS, May 13, 2003; 100(10): 5823 - 5827.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
J Kimber, B N McLean, M Prevett, and S R Hammans
Allgrove or 4 "A" syndrome: an autosomal recessive syndrome causing multisystem neurological disease
J. Neurol. Neurosurg. Psychiatry, May 1, 2003; 74(5): 654 - 657.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
M. de Carvalho, H. Houlden, C. Goizet, and D. Lacombe
Progressive bulbospinal amyotrophy in triple A syndrome with AAAS gene mutation
Neurology, December 10, 2002; 59(11): 1823 - 1823.
[Full Text] [PDF]

Home page
 BrainHome page
H. Houlden, S. Smith, M. de Carvalho, J. Blake, C. Mathias, N. W. Wood, and M. M. Reilly
Clinical and genetic characterization of families with triple A (Allgrove) syndrome
Brain, December 1, 2002; 125(12): 2681 - 2690.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Biol.Home page
J. M. Cronshaw, A. N. Krutchinsky, W. Zhang, B. T. Chait, and M. J. Matunis
Proteomic analysis of the mammalian nuclear pore complex
J. Cell Biol., September 3, 2002; 158(5): 915 - 927.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
R. W. Orrell and A. J.L. Clark
ALADIN, but where's the Genie?
Neurology, March 26, 2002; 58(6): 847 - 848.
[Full Text] [PDF]

Home page
 NeurologyHome page
C. Goizet, B. Catargi, F. Tison, A. Tullio-Pelet, S. Hadj-Rabia, F. Pujol, A. Lagueny, S. Lyonnet, and D. Lacombe
Progressive bulbospinal amyotrophy in Triple A syndrome with AAAS gene mutation
Neurology, March 26, 2002; 58(6): 962 - 965.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
F. Sandrini, C. Farmakidis, L. S. Kirschner, S.-M. Wu, A. Tullio-Pelet, S. Lyonnet, D. L. Metzger, C. J. Bourdony, D. Tiosano, W.-Y. Chan, et al.
Spectrum of Mutations of the AAAS Gene in Allgrove Syndrome: Lack of Mutations in Six Kindreds with Isolated Resistance to Corticotropin
J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5433 - 5437.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.