The Prevalence of GNAS Deficiency-Related Diseases in a Large Cohort of Patients Characterized by the EuroPHP Network.
J Clin Endocrinol Metab
; 101(10): 3657-3668, 2016 10.
Article
em En
| MEDLINE
| ID: mdl-27428667
ABSTRACT
CONTEXT The term pseudohypoparathyroidism (PHP) was coined to describe the clinical condition resulting from end-organ resistance to parathormone (rPTH), caused by genetic and/or epigenetic alterations within or upstream of GNAS. Although knowledge about PHP is growing, there are few data on the prevalence of underlying molecular defects. OBJECTIVE:
The purpose of our study was to ascertain the relative prevalence of PHP-associated molecular defects.DESIGN:
With a specially designed questionnaire, we collected data from all patients (n = 407) clinically and molecularly characterized to date by expert referral centers in France, Italy, and Spain.RESULTS:
Isolated rPTH (126/407, 31%) was caused only by epigenetic defects, 70% of patients showing loss of imprinting affecting all four GNAS differentially methylated regions and 30% loss of methylation restricted to the GNAS A/BTSS-DMR. Multihormone resistance with no Albright's hereditary osteodystrophy (AHO) signs (61/407, 15%) was essentially due to epigenetic defects, although 10% of patients had point mutations. In patients with rPTH and AHO (40/407, 10%), the rate of point mutations was higher (28%) and methylation defects lower (about 70%). In patients with multihormone resistance and AHO (155/407, 38%), all types of molecular defects appeared with different frequencies. Finally, isolated AHO (18/407, 4%) and progressive osseous heteroplasia (7/407, 2%) were exclusively caused by point mutations.CONCLUSION:
With European data, we have established the prevalence of various genetic and epigenetic lesions in PHP-affected patients. Using these findings, we will develop objective criteria to guide cost-effective strategies for genetic testing and explore the implications for management and prognosis.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hormônio Paratireóideo
/
Pseudo-Hipoparatireoidismo
/
Subunidades alfa Gs de Proteínas de Ligação ao GTP
Tipo de estudo:
Clinical_trials
/
Prevalence_studies
/
Prognostic_studies
/
Qualitative_research
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
/
Male
País/Região como assunto:
Europa
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article