Coexistence of two different pseudohypoparathyroidism subtypes (Ia and Ib) in the same kindred with independent Gsα coding mutations and GNAS imprinting defects

B. Lecumberri, E. Fernández-Rebollo, L. Sentchordi, P. Saavedra, A. Bernal-Chico, L. F. Pallardo, J. M. Jiménez Bustos, L. Castaño, M. De Santiago, O. Hiort, Guiomar Pérez De Nanclares*, Murat Bastepe

*Korrespondierende/r Autor/-in für diese Arbeit
37 Zitate (Scopus)

Abstract

Background: Pseudohypoparathyroidism (PHP) defines a rare group of disorders whose common feature is resistance to the parathyroid hormone. Patients with PHP-Ia display additional hormone resistance, Albright hereditary osteodystrophy (AHO) and reduced Gsα activity in easily accessible cells. This form of PHP is associated with heterozygous inactivating mutations in Gsα-coding exons of GNAS, an imprinted gene locus on chromosome 20q13.3. Patients with PHP-Ib typically have isolated parathyroid hormone resistance, lack AHO features and demonstrate normal erythrocyte Gsα activity. Instead of coding Gsα mutations, patients with PHP-Ib display imprinting defects of GNAS, caused, at least in some cases, by genetic mutations within or nearby this gene. Patients: Two unrelated PHP families, each of which includes at least one patient with a Gsα coding mutation and another with GNAS loss of imprinting, are reported here. Results: One of the patients with GNAS imprinting defects has paternal uniparental isodisomy of chromosome 20q, explaining the observed imprinting abnormalities. The identified Gsa coding mutations include a tetranucleotide deletion in exon 7, which is frequently found in PHP-Ia, and a novel single nucleotide change at the acceptor splice junction of intron 11. Conclusions: These molecular data reveal an interesting mixture, in the same family, of both genetic and epigenetic mutations of the same gene.

OriginalspracheEnglisch
ZeitschriftJournal of Medical Genetics
Jahrgang47
Ausgabenummer4
Seiten (von - bis)276-280
Seitenumfang5
ISSN0022-2593
DOIs
PublikationsstatusVeröffentlicht - 04.2010

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

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