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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/35155

Title: Pseudohypoparathyroidism Type Ib Associated with Novel Duplications in the GNAS Locus
Authors: Pérez-Nanclares, Gustavo
Velayos, Teresa
Vela, Amaya
Muñoz Torres, Manuel
Castaño, Luis
Issue Date: 2015
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 ~320 kb, occurred ‘de novo’ in the patient, whereas the other one, of ~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.
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/r4​3-2591/es). TV is supported by the FPI Program of the University of Basque Country (UPV-EHU, http://www.ehu.es/p200-home/es).
Publisher: Public Library of Science (PLOS)
Keywords: Genetic loci
Polymerase chain reaction
Comparative genomics
Genome analysis
DNA methylation
Genomic imprinting
Thyroid-stimulating hormone
URI: http://hdl.handle.net/10481/35155
ISSN: 1932-6203
Rights : Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License
Citation: Pérez-Nanclares, G. Pseudohypoparathyroidism Type Ib Associated with Novel Duplications in the GNAS Locus. Plos One, 10(2): e0117691 (2015). [http://hdl.handle.net/10481/35155]
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