This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mantovani, G. Articles by Spada, A. Search for Related Content PubMed PubMed Citation Articles by Mantovani, G. Articles by Spada, A.

Mutational Analysis of GNAS1 in Patients with Pseudohypoparathyroidism: Identification of Two Novel Mutations¹

Ospedale Maggiore IRCCS, Institute of Endocrine Sciences (G.M., R.R., P.B.-P., A.S.), and Pediatric Department, Endocrine Unit, Scientific Ospedale S. Raffaele (G.W., S.B.), University of Milan, and Pediatric Department, Ospedale Buzzi (V.B.), 20122 Milan; and First Divisione Medica, Ospedale Regionale Veneto (E.D.M.), 31100 Treviso, Italy

Address all correspondence and requests for reprints to: Dr. Anna Spada, Istituto di Scienze Endocrine, Padiglione Granelli, Ospedale Maggiore IRCCS, Via Francesco Sforza 35, 20122 Milan, Italy. E-mail: endosci{at}mailserver.unimi.it

Pseudohypoparathyroidism (PHP) refers to two major variants that generally coexist in the same family, PHP type Ia (PHP Ia), in which both PTH resistance and a constellation of physical features, termed Albright’s hereditary osteodystrophy (AHO), are present, and pseudopseudohypoparathyroidism (PPHP), in which AHO occurs without PTH resistance. Most patients with PHP Ia show a partial deficiency (50%) of G_s activity, due to loss of function mutations in G_s gene (GNAS1). The present study reports clinical, biochemical, and molecular data of 8 unrelated families with PHP Ia and PPHP. The 13 exons of GNAS1 were screened for mutations by PCR and direct sequencing of the amplified products. We detected heterozygous mutations in the affected members of the 4 families in which PHP Ia was present. In 2 families 2 previously reported deletions in exons 5 and 7 were found, whereas in the other 2 families, 2 novel frameshift deletions were identified in exons 1 and 11, causing a premature stop codon in the mutant allele. No mutation was detected in the families in which PPHP was the only clinical manifestation.

In conclusion, we report the first mutational analysis of Italian patients with PHP Ia and PPHP, and we describe two novel deletions in GNAS1. Furthermore, we confirm that these mutations cannot be detected in families with isolated PPHP, suggesting that these forms of AHO are genetically distinct from PHP Ia.

This article has been cited by other articles:

				A. Plagge, G. Kelsey, and E. L Germain-Lee Physiological functions of the imprinted Gnas locus and its protein variants G{alpha}s and XL{alpha}s in human and mouse J. Endocrinol., February 1, 2008; 196(2): 193 - 214. [Abstract] [Full Text] [PDF]

				F. G Riepe, W. Ahrens, N. Krone, R. Folster-Holst, J. Brasch, W. G Sippell, O. Hiort, and C.-J. Partsch Early manifestation of calcinosis cutis in pseudohypoparathyroidism type Ia associated with a novel mutation in the GNAS gene Eur. J. Endocrinol., April 1, 2005; 152(4): 515 - 519. [Abstract] [Full Text] [PDF]

				G. Mantovani, S. Bondioni, M. Locatelli, C. Pedroni, A. G. Lania, E. Ferrante, M. Filopanti, P. Beck-Peccoz, and A. Spada Biallelic Expression of the Gs{alpha} Gene in Human Bone and Adipose Tissue J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6316 - 6319. [Abstract] [Full Text] [PDF]

				G. Mantovani, S. Bondioni, A. G. Lania, S. Corbetta, L. de Sanctis, M. Cappa, E. Di Battista, P. Chanson, P. Beck-Peccoz, and A. Spada Parental Origin of Gs{alpha} Mutations in the McCune-Albright Syndrome and in Isolated Endocrine Tumors J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 3007 - 3009. [Abstract] [Full Text] [PDF]

				G. Mantovani, M. Maghnie, G. Weber, E. De Menis, V. Brunelli, M. Cappa, P. Loli, P. Beck-Peccoz, and A. Spada Growth Hormone-Releasing Hormone Resistance in Pseudohypoparathyroidism Type Ia: New Evidence for Imprinting of the Gs{alpha} Gene J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4070 - 4074. [Abstract] [Full Text] [PDF]

				J. Liu, B. Erlichman, and L. S. Weinstein The Stimulatory G Protein {alpha}-Subunit Gs{alpha} Is Imprinted in Human Thyroid Glands: Implications for Thyroid Function in Pseudohypoparathyroidism Types 1A and 1B J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4336 - 4341. [Abstract] [Full Text] [PDF]

				G. Mantovani, E. Ballare, E. Giammona, P. Beck-Peccoz, and A. Spada The Gs{alpha} Gene: Predominant Maternal Origin of Transcription in Human Thyroid Gland and Gonads J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4736 - 4740. [Abstract] [Full Text] [PDF]

				L. S. WEINSTEIN, M. CHEN, and J. LIU Gs{alpha} Mutations and Imprinting Defects in Human Disease Ann. N.Y. Acad. Sci., June 1, 2002; 968(1): 173 - 197. [Abstract] [Full Text] [PDF]

				A. Linglart, J. C. Carel, M. Garabedian, T. Le, E. Mallet, and M. L. Kottler GNAS1 Lesions in Pseudohypoparathyroidism Ia and Ic: Genotype Phenotype Relationship and Evidence of the Maternal Transmission of the Hormonal Resistance J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 189 - 197. [Abstract] [Full Text] [PDF]

				L. S. Weinstein, S. Yu, D. R. Warner, and J. Liu Endocrine Manifestations of Stimulatory G Protein {alpha}-Subunit Mutations and the Role of Genomic Imprinting Endocr. Rev., October 1, 2001; 22(5): 675 - 705. [Abstract] [Full Text] [PDF]

				W. Ahrens, O. Hiort, P. Staedt, T. Kirschner, C. Marschke, and K. Kruse Analysis of the GNAS1 Gene in Albright's Hereditary Osteodystrophy J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4630 - 4634. [Abstract] [Full Text] [PDF]