Reduced bone mineral density and hyaloid vasculature remnants in a consanguineous recessive FEVR family with a mutation in LRP5

• Published in: British journal of ophthalmology 2006-09, Vol.90 (9), p.1163-1167
• Main Authors: Downey, L M, Bottomley, H M, Sheridan, E, Ahmed, M, Gilmour, D F, Inglehearn, C F, Reddy, A, Agrawal, A, Bradbury, J, Toomes, C
• Format: Article
• Language: English
• Subjects: Adolescent; Amino Acid Sequence; Base Sequence; Biological and medical sciences; BMD; Bone density; Bone Density - genetics; bone mineral density; Child; Clinical Science - Extended Report; Defects; DEXA; DNA Mutational Analysis - methods; dual energy x ray absorptiometry; EUA; examination under anaesthesia; Eye Diseases, Hereditary - complications; Eye Diseases, Hereditary - genetics; familial exudative vitreoretinopathy; Families & family life; Female; FEVR; Genes; Genetic Linkage; Genomes; Humans; hyaloid vasculature; Investigative techniques, diagnostic techniques (general aspects); LDL-Receptor Related Proteins - genetics; Low Density Lipoprotein Receptor-Related Protein-5; Low density lipoprotein receptors; LRP5; Male; Medical sciences; Miscellaneous; Molecular Sequence Data; Mutation; Mutation, Missense; Ophthalmology; OPPG; Osteoarticular system. Muscles; Osteoporosis; Osteoporosis - complications; Osteoporosis - genetics; osteoporosis pseudoglioma syndrome; Patients; PCR; Pedigree; persistent hyperplastic primary vitreous; PHPV; polymerase chain reaction; Population; Proteins; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Retinal Diseases - complications; Retinal Diseases - genetics; Standard deviation; Studies
• ISSN: 0007-1161; 1468-2079
• DOI: 10.1136/bjo.2006.092114

Background/aims: Familial exudative vitreoretinopathy (FEVR) is an inherited blinding condition characterised by abnormal development of the retinal vasculature. FEVR has multiple modes of inheritance, and homozygous mutations in LRP5 have recently been reported as underlying the recessive form of this disease. The aim of this study was to examine LRP5 in a consanguineous recessive FEVR family and to clarify the eye and bone phenotype associated with recessive FEVR. Methods: All family members were examined by slit lamp biomicroscopy and indirect ophthalmoscopy. Linkage to LRP5 was determined by genotyping microsatellite markers, constructing haplotypes and calculating lod scores. Mutation screening of LRP5 was performed by polymerase chain reaction amplification of genomic DNA followed by direct sequencing. Bone mineral density (BMD) was evaluated in all family members using dual energy x ray absorptiometry (DEXA). Results: The clinical features observed in this family were consistent with a diagnosis of recessive FEVR. A homozygous LRP5 missense mutation, G550R, was identified in all affected individuals and all unaffected family members screened were heterozygous carriers of this mutation. Reduced BMD, hyaloid vasculature remnants, and nystagmus were features of the phenotype. Conclusion: Recessive mutations in LRP5 can cause FEVR with reduced BMD and hyaloid vasculature remnants. Assessment of a patient with a provisional diagnosis of FEVR should therefore include investigation of BMD, with reduced levels suggestive of an underlying LRP5 mutation.