Endocrine Abstracts

Genomic imprinting is an epigenetic mechanism by which a subset of our genes displays unequal expression of the maternal and paternal alleles; in many cases, one allele is fully silenced. It occurs because these genes are marked differently (by DNA methylation and/or histone modifications) in male and female gametes. These gamete-specific marks are maintained at fertilisation and perpetuated throughout development and adult life, such that the alleles of imprinted genes retain...

The two main subtypes of pseudohypoparathyroidism (PHP), PHP-Ia and -Ib, are caused by mutations in GNAS exons 1–13 and methylation defects in the imprinted GNAS cluster, respectively. PHP-Ia patients show Albright hereditary osteodystrophy (AHO), together with end-organ resistance to the action of different hormones that activate the Gs-coupled pathways, primarily PTH, TSH, gonadotropins, and GHRH. In PHP-Ib patients AHO is classically absent, Gsα acti...

The GNAS locus is a complex imprinted locus which encodes Gsa and four additional alternative transcripts including Xlas. Gsa is the ubiquitous α-subunit of the G-protein involved in major biological pathways including hormonal signaling and cell differentiation. Xlas is the only transcript sharing with Gsa the protein domain encoded by GNAS exons 2 to 13 of, which plays a key role in coupling activated receptors to adenylate cyclase stimulation. However, Xl...