P12.13: Prenatal presentation and postnatal evolution of a patient with Jansen metaphyseal dysplasia with a novel missense mutation in PTH1R

weekfemalefetus.Atbirth,skeletalradiographsshowedmarkedhypomineralizationandsuggestedhypophosphatasia.However,elevatedbloodcalciumandalkalinephosphataseexcludedhypo-phosphatasia and raised the possibility of Jansen metaphysealdysplasia. Molecular analysis of the PTH/PTHrP receptor gene(PTH1R) showed heterozygosity for a previously undescribedtransversion variant (c.1373T>A), which predicts p.Ile458Lys.In vitro evaluation of wild type and mutant PTH/PTHrP recep-tors supported the pathogenic role of the p.Ile458Lys substitu-tion, and confirmed the diagnosis of Jansen metaphysealdysplasia. This disorder may present prenatally with wavy ribsandinthenewbornwithhypomineralization,andmaythereforebe confused with hypophosphatasia. The mottled metaphyseallesions typically associated with this disease appear only inchildhood.