Mutational analysis of GNAS1 in patients with pseudohypoparathyroidism: identification of two novel mutations
Articolo
Data di Pubblicazione:
2000
Citazione:
Mutational analysis of GNAS1 in patients with pseudohypoparathyroidism: identification of two novel mutations / G. Mantovani, R. Romoli, G. Weber, V. Brunelli, E. De Menis, S. Beccio, P. Beck-Peccoz, A. Spada. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - 85:11(2000 Nov), pp. 4243-4248.
Abstract:
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 Gs activity, due to loss of function mutations in Gsalpha 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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Albright hereditary osteodystrophy; GS-alpha gene; necleotide regulatory protein; stimulatory G-protein; G(S)alpha gene; deficient activity; deletion mutation; adenylyl-cyclase; G(S-alpha); endocrine
Elenco autori:
G. Mantovani, R. Romoli, G. Weber, V. Brunelli, E. De Menis, S. Beccio, P. Beck-Peccoz, A. Spada
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