Abstract
Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive disorder characterized by severe osteoporosis and eye abnormalities that lead to vision loss. In this study, clinical findings and genetic study of two siblings with OPPG are presented. Whole exome sequencing of DNA enriched for exonic regions was performed with SureSelect 38Mbp all exon kit v. 7.0. The two siblings presented with different clinical manifestations of OPPG. The younger female sibling had blindness and severe osteoporosis with multiple fractures, while her older brother was also blind but with less severe osteoporosis and no fractures. On analysis, a novel homozygous nonsense mutation (c.351G>A) in exon 2 of LRP5 (NM_002335) was found, predicted to change a tryptophan at 117 to a stop codon (p. Trp117Ter). Thus, a variable phenotype was associated with an identical variant in these two siblings. The novel mutation reported herein expands the spectrum of the underlying genetic pathology of OPPG.