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Vol. 77, No. 2, 2012
Issue release date: April 2012
Section title: Original Paper
Horm Res Paediatr 2012;77:115–120
(DOI:10.1159/000336193)

Osteoporosis-Pseudoglioma Syndrome: Three Novel Mutations in the LRP5 Gene and Response to Bisphosphonate Treatment

Tüysüz B. · Bursalı A. · Alp Z. · Suyugül N. · Laine C.M. · Mäkitie O.
Departments of aPediatric Genetics and bOphthalmology, Cerrahpaşa Medical School, Istanbul University, and cBaltalimanı Metin Sabanci Bone Diseases Education and Research Hospital, Istanbul, Turkey; dFolkhälsan Institute of Genetics, Biomedicum Helsinki, and ePediatric Endocrinology and Metabolic Bone Diseases, Children’s Hospital, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 8/9/2011 8:52:35 AM
Accepted: 1/2/2012
Published online: 3/23/2012

Number of Print Pages: 6
Number of Figures: 2
Number of Tables: 0

ISSN: 1663-2818 (Print)
eISSN: 1663-2826 (Online)

For additional information: http://www.karger.com/HRP

Abstract

Background/Aims: 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). Methods/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. Conclusion: 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.


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 8/9/2011 8:52:35 AM
Accepted: 1/2/2012
Published online: 3/23/2012

Number of Print Pages: 6
Number of Figures: 2
Number of Tables: 0

ISSN: 1663-2818 (Print)
eISSN: 1663-2826 (Online)

For additional information: http://www.karger.com/HRP


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Ai M, Heeger S, Bartels CF, Schelling DK: Clinical and molecular findings in osteoporosis-pseudoglioma syndrome. Am J Hum Genet 2005;77:741–753.
  2. Cheung WM, Jin LY, Smith DK, Cheung PT, Kwan EY, Low L, Kung AW: A family with osteoporosis pseudoglioma syndrome due to compound heterozygosity of two novel mutations in the LRP5 gene. Bone 2006;39:470–476.
  3. Marques-Pinheiro A, Levasseur R, Cormier C, Bonneau J, Boileau C, Varret M, Abifadel M, Allanore Y: Novel LRP5 gene mutation in a patient with osteoporosis-pseudoglioma syndrome. Joint Bone Spine 2010;77:151–153.
  4. Narumi S, Numakura C, Shiihara T, Seiwa C, Nozaki Y, Yamagata T, Momoi MY, Watanabe Y, Yoshino M, Matsuishi T, Nishi E, Kawame H, Akahane T, Nishimura G, Emi M, Hasegawa T: Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: identification of a 7.2-kb microdeletion using oligonucleotide tiling microarray. Am J Med Genet A 2010;152A:133–140.
  5. Laine CM, Chung BD, Susic M, Prescott T, Semler O, Fiskerstrand T, D’Eufemia P, Castori M, Pekkinen M, Sochett E, Cole WG, Netzer C, Mäkitie O: Novel mutations affecting LRP5 splicing in patients with osteoporosis-pseudoglioma syndrome (OPPG). Eur J Hum Genet 2011;19:875–881.
  6. Gong Y, Vikkula M, Boon L, Liu J, Beighton P, Ramesar R, Peltonen L, Somer H, Hirose T, Dallapiccola B, De Paepe A, Swoboda W, Zabel B, Superti-Furga A, Steinmann B, Brunner HG, Jans A, Boles RG, Adkins W, van den Boogaard MJ, Olsen BR, Warman ML: Osteoporosis-pseudoglioma syndrome, a disorder affecting skeletal strength and vision, is assigned to chromosome region 11q12–13. Am J Hum Genet 1996;59:146–151.
  7. Gong Y, Slee RB, Fukai N, Warman ML, Osteoporosis-Pseudoglioma Syndrome Collaborative Group: LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 2001;107:513–523.
  8. Lobov IB, Rao S, Carroll TJ, Vallance JE, Ito M, Ondr JK, Kurup S, Glass JA, Patel MS, Shu W, Morrisey EE, McMahon AP, Karsenty G, Lang R: WNT7b mediates macrophage-induced programmed cell death in patterning of the vasculature. Nature 2005;437:417–421.
  9. Ye X, Wang Y, Cahill H, Yu M, Beadea TC, Smallwood PM, Peachey NS, Nathens J: Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization. Cell 2009;139:285–298.
  10. Levasseur R, Lacombe D, de Vernejoul MC: LRP5 mutations in osteoporosis-pseudoglioma syndrome and high-bone-mass disorders. Joint Bone Spine 2005;72:207–214.

    External Resources

  11. Kato M, Patel MS, Levasseur R, Lobov I, Chang BH, Glass DA, Hartmann C, Li L, Hwang TH, Brayton CF, Lang RA, Karsenty G, Chan L: Cbfa1-independent decrease in osteoblast proliferation, osteopenia,and persistent embryonic eye vascularization in mice deficient in LRP5, a Wnt co-receptor. J Cell Biol 2002;157:303–314.
  12. Saarinen A, Saukkonen T, Kivela T, Lahtinen U, Laine C, Somer M, Toiviainen-Salo S, Cole WG, Lehesjoki AE, Makitie O: LDL receptor-related protein 5 (LRP5) mutations and osteoporosis, impaired glucose metabolism and hypercholesterolaemia. Clin Endocrinol 2010;72:481–488.
  13. Streeten EA, McBride D, Puffenberger E, Hoffman ME, Pollin TI, Donnelly P, Sack P, Morton H: Osteoporosis-pseudoglioma syndrome: description of 9 new cases and beneficial response to bisphosphonates. Bone 2008;43:584–590.
  14. Zacharin M, Cundy T: Osteoporosis pseudoglioma syndrome: treatment of spinal osteoporosis with intravenous bisphosphonates. J Pediatr 2000;137:410–415.
  15. Levasseur R: Treatment and management of osteoporosis-pseudoglioma syndrome. Expert Rev Endocrinol Metab 2008;3:337–348.
  16. McDowell CL, Moore JD: Multiple fractures in a child: the osteoporosis pseudoglioma syndrome. J Bone Joint Surg Am 1992;74:1247–1249.
  17. Somer H, Palotie A, Somer M, Hoikka V, Peltonen L: Osteoporosis-pseudoglioma syndrome: clinical, morphological, and biochemical studies. J Med Genet 1988;25:543–549.