title: Novel LRP5 gene mutation in a patient with osteoporosis-pseudoglioma syndrome.
abstract: Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive disorder characterised by severe juvenile-onset osteoporosis and congenital or early-onset blindness. This serious illness is due to mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) that is a major actor in pathways involved in bone remodelling. Here, we report a novel frameshift mutation identified in a 22 year-old Tunisian boy of a consanguineous family. This patient had low bone mineral density (BMD), experienced multiple fractures during childhood and suffered ocular alterations with blindness. Direct DNA sequencing showed a homozygous 5 base pair insertion in exon 5 of the LRP5 gene. This new mutation is located in the first EGF-like domain and gives rise to a truncated protein of 384 amino acids. The functional significance of this mutation clearly indicates a loss-of-function mutation of the LRP5 gene leading to the observed OPPG phenotype. Rheumatologists must be aware of LRP5 gene that in addition to being a major gene in the mendelian disease that is OPPG syndrome seems to be involved in osteoporosis in the general population through some of its polymorphisms.
authors.affiliation: Inserm U781, Paris Descartes University, Necker Hospital, Paris, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Marques-Pinheiro
authors.forename: Régis
authors.initials: R
authors.lastname: Levasseur
authors.forename: Catherine
authors.initials: C
authors.lastname: Cormier
authors.forename: Jessica
authors.initials: J
authors.lastname: Bonneau
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
authors.forename: Mathilde
authors.initials: M
authors.lastname: Varret
authors.forename: Marianne
authors.initials: M
authors.lastname: Abifadel
authors.forename: Yannick
authors.initials: Y
authors.lastname: Allanore
mesh_terms: D001766:Blindness / Q000235:genetics*; D015519:Bone Density / Q000235:genetics; D050723:Fractures, Bone / Q000235:genetics*; D016368:Frameshift Mutation; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008297:Male; D010024:Osteoporosis / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013577:Syndrome; D055815:Young Adult
chemical_list: D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5