Clinical and neurobiological findings, treatment developments in Late-Life Depression

摘要

Background:GNAS encodes the subunit of the stimulatory G protein (Gs). Maternal inherited Gs mutations cause pseudohypoparathyroidism type Ia (PHP-Ia), associated with shortening of the 4th and 5th metacarpals. Aims: Here we investigated the Gs pathway in short patients with distinct shortening of the 4th and 5th metacarpals. Methods: In 571 children with short stature and 4 patients with PHP-Ia metacarpal bone lengths were measured. In identified patients we analysed the Gs protein function in platelets, performed GNAS sequencing, and epigenetic analysis of four significant differentially methylated regions. Results: In 51 patients (8.9%) shortening of the 4th and 5th metacarpals was more pronounced than their height deficit. No GNAS coding mutations were identified in 20 analysed patients, except in 2 PHP-Ia patients. Gs activity was reduced in all PHP-Ia patients and in 25% of the analysed patients. No significant methylation changes were identified. Conclusions: Our findings suggest that patients with short stature and distinct metacarpal bone shortening could be part of the wide variety of PHP/PPHP, therefore it was worthwhile analysing the Gs protein function and GNAS gene in these patients in order to further elucidate the phenotype and genotype of Gs dysfunction.