New Splice Site Acceptor Mutation in AIRE Gene in Autoimmune Polyendocrine Syndrome Type 1
Mora, Mireia (Hospital Clínic i Provincial de Barcelona)
Hanzu, Felicia A. (Hospital Clínic i Provincial de Barcelona)
Pradas-Juni, Marta (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Aranda, Gloria (Hospital Clínic i Provincial de Barcelona)
Halperin, Irene (Hospital Clínic i Provincial de Barcelona)
Puig Domingo, Manuel (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Aguiló, Sira (Hospital Clínic i Provincial de Barcelona)
Fernández-Rebollo, Eduardo (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Universitat Autònoma de Barcelona. Departament de Medicina

Data:	2014
Resum:	Autoimmune polyglandular syndrome type 1 (APS-1, OMIM 240300) is a rare autosomal recessive disorder, characterized by the presence of at least two of three major diseases: hypoparathyroidism, Addison's disease, and chronic mucocutaneous candidiasis. We aim to identify the molecular defects and investigate the clinical and mutational characteristics in an index case and other members of a consanguineous family. We identified a novel homozygous mutation in the splice site acceptor (SSA) of intron 5 (c. 653-1G>A) in two siblings with different clinical outcomes of APS-1. Coding DNA sequencing revealed that this AIRE mutation potentially compromised the recognition of the constitutive SSA of intron 5, splicing upstream onto a nearby cryptic SSA in intron 5. Surprisingly, the use of an alternative SSA entails the uncovering of a cryptic donor splice site in exon 5. This new transcript generates a truncated protein (p. A214fs67X) containing the first 213 amino acids and followed by 68 aberrant amino acids. The mutation affects the proper splicing, not only at the acceptor but also at the donor splice site, highlighting the complexity of recognizing suitable splicing sites and the importance of sequencing the intron-exon junctions for a more precise molecular diagnosis and correct genetic counseling. As both siblings were carrying the same mutation but exhibited a different APS-1 onset, and one of the brothers was not clinically diagnosed, our finding highlights the possibility to suspect mutations in the AIRE gene in cases of childhood chronic candidiasis and/or hypoparathyroidism otherwise unexplained, especially when the phenotype is associated with other autoimmune diseases.
Ajuts:	Ministerio de Ciencia e Innovación SAF2010-19527 Ministerio de Ciencia e Innovación BES-2011-044579 European Commission 229673
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PloS one, Vol. 9 (july 2014) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0101616
PMID: 24988226

9 p, 1.1 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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