dc.contributor.author | Pérez de Nanclares, Gustavo | |
dc.contributor.author | Velayos Gainza, Teresa | |
dc.contributor.author | Vela Desojo, Amaia | |
dc.contributor.author | Muñoz-Torres, Manuel | |
dc.contributor.author | Castaño González, Luis Antonio | |
dc.date.accessioned | 2016-05-05T10:52:59Z | |
dc.date.available | 2016-05-05T10:52:59Z | |
dc.date.issued | 2015-02-24 | |
dc.identifier.citation | Plos One 10(2) : (2015) // Article ID e0117691 | es |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/10810/18164 | |
dc.description.abstract | Context
Pseudohypoparathyroidism type 1b (PHP-Ib) is characterized by renal resistance to PTH (and, sometimes, a mild resistance to TSH) and absence of any features of Albright's hereditary osteodystrophy. Patients with PHP-Ib suffer of defects in the methylation pattern of the complex GNAS locus. PHP-Ib can be either sporadic or inherited in an autosomal dominant pattern. Whereas familial PHP-Ib is well characterized at the molecular level, the genetic cause of sporadic PHP-Ib cases remains elusive, although some molecular mechanisms have been associated with this subtype.
Objective
The aim of the study was to investigate the molecular and imprinting defects in the GNAS locus in two unrelated patients with PHP-Ib.
Design
We have analyzed the GNAS locus by direct sequencing, Methylation-Specific Multiplex Ligation-dependent Probe Amplification, microsatellites, Quantitative Multiplex PCR of Short Fluorescent fragments and array-Comparative Genomic Hybridization studies in order to characterize two unrelated families with clinical features of PHP-Ib.
Results
We identified two duplications in the GNAS region in two patients with PHP-Ib: one of them, comprising similar to 320 kb, occurred 'de novo' in the patient, whereas the other one, of similar to 179 kb in length, was inherited from the maternal allele. In both cases, no other known genetic cause was observed.
Conclusion
In this article, we describe the to-our-knowledge biggest duplications reported so far in the GNAS region. Both are associated to PHP-Ib, one of them occurring 'de novo' and the other one being maternally inherited. | es |
dc.description.sponsorship | This work was partially supported by Grants IT-795-13 and IT-472-07 from the Basque Department of Education (http://www.hezkuntza.ejgv.euskadi.net/r43-2591/es). TV is supported by the FPI Program of the University of Basque Country (UPVEHU, http://www.ehu.es/p200-home/es). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | es |
dc.language.iso | eng | es |
dc.publisher | Public Library Science | es |
dc.rights | info:eu-repo/semantics/openAccess | es |
dc.subject | albrights hereditary osteodistrophy | es |
dc.subject | imprinting control element | es |
dc.subject | GS-alpha gene | es |
dc.subject | epigenetic defects | es |
dc.subject | hormone resistance | es |
dc.subject | deletion | es |
dc.subject | mutations | es |
dc.subject | A/B | es |
dc.subject | disorders | es |
dc.subject | subunit | es |
dc.title | Pseudohypoparathyroidism Type Ib Associated with Novel Duplications in the GNAS Locus | es |
dc.type | info:eu-repo/semantics/article | es |
dc.rights.holder | © 2015 Perez-Nanclares et al. This is an
open access article distributed under the terms of the
Creative Commons Attribution License
, which permits
unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are
credited | es |
dc.relation.publisherversion | http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0117691#abstract0 | es |
dc.identifier.doi | 10.1371/journal.pone.0117691 | |
dc.departamentoes | Pediatría | es_ES |
dc.departamentoeu | Pediatria | es_ES |
dc.subject.categoria | AGRICULTURAL AND BIOLOGICAL SCIENCES | |
dc.subject.categoria | BIOCHEMISTRY AND MOLECULAR BIOLOGY | |
dc.subject.categoria | MEDICINE | |