Journal
BONE
Volume 43, Issue 3, Pages 584-590Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2008.04.020
Keywords
osteoporosis-pseudoglioma; compound heterozygote; juvenile osteoporosis; blindness; LRP5
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Funding
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR016500] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK072488] Funding Source: NIH RePORTER
- NCRR NIH HHS [M01 RR016500-030010, M01 RR016500] Funding Source: Medline
- NIDDK NIH HHS [P30 DK072488, P30 DK072488-07, P30 DK072488-059001] Funding Source: Medline
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Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive disorder of severe juvenile osteoporosis and congenital blindness, due to mutations in the low-density lipoprotein receptor-related Protein 5 (LRP5) gene. Approximately fifty cases of OPPG have been reported. We report 9 new cases of OPPG, in three related nuclear families of Conservative Mennonites in Pennsylvania. All 9 children with OPPG were blind and had osteoporosis. Four of six parents had low bone mineral density (BMD) or osteoporosis: 2 were normal. Sequence analysis from genomic DNA revealed homozygosity for a nonsense mutation of exon 6 of LRP5 (W425X) in four OPPG cases tested in families A and C. In family 13, OPPG cases were compound heterozygotes for the exon 6 W425X LRP5 Mutation and a second exon 6 mutation (T409A): bone phenotype was milder than in family A. Neither of these mutations was present in an unrelated normal. The four treated OPPG patients all responded to bisphosphonates (duration 1.5-6.5 years) with improvement in Z-scores. One patient had a negligible response to teriparatide. In Summary, we report 9 new cases Of OPPG due to two novel LRP5 Mutations, note a milder bone phenotype but similar Ocular phenotype in LRP5 W425X/T409A Compound heterozygotes than in W425X homozygotes and describe positive response to bisphosphonate treatment in lour cases. (C) 2008 Elsevier Inc. All rights reserved.
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