Osteoporosis-Pseudoglioma in a Mauritanian Child due to a Novel Mutation in LRP5.

Noura Biha,M M Hacen,Corinne Collet,S M Ghaber

doi:10.1155/2016/9814928

Abstract

Osteoporosis-pseudoglioma (OPPG) syndrome is a very rare autosomal recessive disorder, caused by mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. It manifests by severe juvenile osteoporosis with congenital or infancy-onset visual loss. We describe a case of OPPG due to novel mutation in LRP5 gene, occurring in a female Mauritanian child. This 10-year-old female child was born blind, and after then multiple fragility fractures appeared. PCR amplification and sequencing revealed a novel homozygous nonsense mutation in exon 10 of the LRP5 gene (c.2270G>A; pTrP757⁎); this mutation leads to the production of a truncated protein containing 757 amino acids instead of 1615, located in the third β-propeller domain of the LRP5 protein. Both parents were heterozygous for the mutation. This is the first case of the OPPG described in black Africans, which broadens the spectrum of LRP5 gene mutations in OPPG.

Highlights

Osteoporosis-pseudoglioma (OPPG) syndrome (OPPG, OMIM 259770) is a very rare autosomal recessive disorder. It combines severe juvenile osteoporosis with congenital blindness. This serious disease is caused by loss-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene [1]
Gong et al [4] had first identified loss of function mutation of the LRP5 gene leading to osteoporosis pseudoglioma (OPPG)
Thirty mutations have been described in OPPG including fourteen homozygous mutations, principally located in the second and third beta-propeller domains of LRP5 [1, 2], which have a high affinity with wnt ligand [5]

Summary

Introduction

Osteoporosis-pseudoglioma (OPPG) syndrome (OPPG, OMIM 259770) is a very rare autosomal recessive disorder It combines severe juvenile osteoporosis with congenital blindness. This serious disease is caused by loss-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene [1]. Gong et al [4] had first identified loss of function mutation of the LRP5 gene leading to osteoporosis pseudoglioma (OPPG). This report concerns a ten-year-old Mauritanian female child, who was referred by orthopedics service for assessment of fragility fractures. She presented with five broken limbs (humerus, wrist, ankle, and femur) after a fall from standing height, which premiered at the age of 5 years. Bone mineral density (BMD) revealed a Z score of −5.5 at the spine

Sequencing Analysis

Results

Discussion