RT Journal Article
T1 Pseudohypoparathyroidism type Ib associated with novel duplications in the GNAS locus.
A1 Perez-Nanclares, Gustavo
A1 Velayos, Teresa
A1 Vela, Amaya
A1 Muñoz-Torres, Manuel
A1 Castaño, Luis
K1 Adulto
K1 Femenino
K1 Subunidades alfa de la Proteína de Unión al GTP Gs
K1 Duplicación de gen
K1 Masculino
K1 Seudohipoparatiroidismo
K1 Adolescente
AB 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 areassociated to PHP-Ib, one of them occurring 'de novo' and the other one being maternally inherited.
PB Public Library of Science
YR 2015
FD 2015-02-24
LK http://hdl.handle.net/10668/2568
UL http://hdl.handle.net/10668/2568
LA en
NO Perez-Nanclares G, Velayos T, Vela A, Muñoz-Torres M, Castaño L. Pseudohypoparathyroidism type Ib associated with novel duplications in the GNAS locus. PLoS ONE; 10(2):e0117691
NO Case Reports; Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 5, 2025