Prenatal presentation and postnatal evolution of a patient with Jansen metaphyseal dysplasia with a novel missense mutation in PTH1R.
Wave-shaped ribs were detected at prenatal ultrasound in a 20(+1) week female fetus. At birth, skeletal radiographs showed marked hypomineralization and suggested hypophosphatasia. However, elevated blood calcium and alkaline phosphatase excluded hypophosphatasia and raised the possibility of Jansen metaphyseal dysplasia. Molecular analysis of the PTH/PTHrP receptor gene (PTH1R) showed heterozygosity for a previously undescribed transversion variant (c.1373T>A), which predicts p.Ile458Lys. In vitro evaluation of wild type and mutant PTH/PTHrP receptors supported the pathogenic role of the p.Ile458Lys substitution, and confirmed the diagnosis of Jansen metaphyseal dysplasia. This disorder may present prenatally with wavy ribs and in the newborn with hypomineralization, and may therefore be confused with hypophosphatasia. The mottled metaphyseal lesions typically associated with this disease appear only in childhood.
Laboratory of Genetic Disorders of Childhood, A. Nocivelli Institute for Molecular Medicine, Department of Pathology, Spedali Civili, Brescia, Italy.
Gianfranco
G
Savoldi
Claudia
C
Izzi
Marino
M
Signorelli
Maria Pia
MP
Bondioni
Chiara
C
Romani
Gaetana
G
Lanzi
Daniele
D
Moratto
Lucio
L
Verdoni
Moira
M
Pinotti
Federico
F
Prefumo
Andrea
A
Superti-Furga
Alba
A
Pilotta
D000328:Adult; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D020125:Mutation, Missense; D010009:Osteochondrodysplasias / Q000175:diagnosis* / Q000235:genetics*; D011247:Pregnancy; D011859:Radiography; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics*; D016216:Ultrasonography, Prenatal
C473449:PTH1R protein, human; D044168:Receptor, Parathyroid Hormone, Type 1
Jansen metaphyseal dysplasia; PTH/PTHrP receptor; PTH1R