title: Osteoporosis-pseudoglioma syndrome: three novel mutations in the LRP5 gene and response to bisphosphonate treatment.
abstract: OBJECTIVE
  Osteoporosis-pseudoglioma (OPPG) syndrome is a rare disorder characterized by congenital or infancy-onset visual loss and severe juvenile osteoporosis. OPPG is caused by homozygous mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. We present three novel homozygous LRP5 mutations found in 3 unrelated Turkish children with consanguineous parents, along with clinical phenotypes and response to treatment with bisphosphonates (bisP).
  
  
  RESULTS
  The LRP5 gene was analyzed by direct sequencing after PCR amplification. Mutation screening for LRP5 revealed homozygous nonsense R1002X mutation in the first patient and homozygous missense mutations V336M and G507S in the second and third patient, respectively. The parents were heterozygous for these mutations. The patients' eye symptoms began during the first months of life but the OPPG diagnoses were made based on skeletal deformities and osteopenia after 4 years of age. The patients' bone mineral density Z scores were very low and consistent with osteopenia. All patients were treated with bisP for 3.5-7 years.
  
  
  CONCLUSIONS
  We report three novel LRP5 mutations in 3 Turkish patients with OPPG. We show that the response of bisP therapy has improved the lumbar spinal bone mineral density Z scores and the patients' quality of life as the bone pains decreased.
authors.affiliation: Department of Pediatric Genetics, Cerrahpaşa Medical School, Istanbul University, Istanbul, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Tüysüz
authors.forename: A
authors.initials: A
authors.lastname: Bursalı
authors.forename: Z
authors.initials: Z
authors.lastname: Alp
authors.forename: N
authors.initials: N
authors.lastname: Suyugül
authors.forename: C M
authors.initials: CM
authors.lastname: Laine
authors.forename: O
authors.initials: O
authors.lastname: Mäkitie
mesh_terms: D019943:Amino Acid Substitution; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D003241:Consanguinity; D004164:Diphosphonates / Q000627:therapeutic use*; D004351:Drug Resistance; D005128:Eye Diseases / Q000188:drug therapy / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010013:Osteogenesis Imperfecta / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D014421:Turkey
chemical_list: D050071:Bone Density Conservation Agents; D018389:Codon, Nonsense; D004164:Diphosphonates; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5