A paternally inherited non-sense variant c.424G>T (p.G142*) in the first exon of XLαs in an adult patient with hypophosphatemia and osteopetrosis.

摘要: XLαs, the extra-large isoform of alpha-subunit stimulatory guanine nucleotide-binding protein (Gsα), is paternally expressed. The significance XLαs in humans remains largely unknown. Here, we report a patient who presented with increased bone mass, hypophosphatemia, and elevated parathyroid hormone (PTH) levels. His serum calcium was lower limit normal range. Whole exome sequencing this subject found novel non-sense variant c.424G>T (p. G142*) first exon which inherited from his father transmitted to daughter. This predicted exclusively influence expression while possibly having no significant effects on other gene products locus. Ellsworth-Howard test revealed renal response PTH proband. Human SaOS2 cells transfected mutant failed generate cyclic adenosine monophosphate under stimulation, indicating skeletal resistance hormone. showed higher circulating sclerostin, dickkopf1, osteoprotegerin (OPG) levels, receptor activator nuclear factor kappa-B ligand/OPG ratio, leading reduced resorption. Our findings indicate that plays critical role metabolism GNAS locus should be considered as candidate for high mass.