A novel nonsense mutation c.424G>T (p. G142X) in the first exon of XLas leading to osteopetrosis

摘要: GNAS is one of the most complex gene loci in human genome and encodes multiple products. XLas, extra-large isoform alpha-subunit stimulatory guanine nucleotide-binding protein (Gas), paternally inherited. Although XLas can mimic action Gas, its significance remains largely unknown humans. Here we report a patient presented with increased bone mass, hypophosphatemia, elevated parathyroid hormone levels. His serum calcium was lower limit normal range. DEXA scan revealed progressive increase density this patient. Whole exome sequencing subject found novel nonsense mutation c.424G>T (p. G142X) first exon which inherited from his father transmitted to daughter. This predicted exclusively influence expression while may have no significant effects on other products locus. SaOS2 cells transfected mutant failed generate cAMP under stimulation, indicating skeletal resistance hormone. showed higher circulating SOST, DKK1 OPG levels, RANKL levels RANKL/OPG ratio, leading reduced resorption. It speculated that belong very rare type pseudohypoparathyroidism selective but renal tubular response Our findings indicate plays critical role metabolism locus should be considered as candidate for high mass.