OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME, A DISORDER AFFECTING SKELETAL STRENGTH AND VISION, IS ASSIGNED TO CHROMOSOME REGION 11Q12-13

Osteoporosis-pseudoglioma syndrome (OPS) is an autosomal recessive dis order characterized by severs juvenile-onset osteoporosis and congenit al or juvenile-onset blindness. The pathogenic mechanism is not known. Clinical, biochemical, and microscopic analyses suggest that OPS may be a disorder of matrix homeostasis rather than a disorder of matrix s tructure. Consequently, identification of the OPS gene and its protein product could provide insights regarding common osteoporotic conditio ns, such as postmenopausal and senile osteoporosis. As a first step to ward determining the cause of OPS, we utilized a combination of tradit ional linkage analysis and homozygosity mapping to assign the OPS locu s to chromosome region 11q12-13. Mapping was accomplished by analyzing 16 DNA samples (seven affected individuals) from three different cons anguineous kindreds. Studies in 10 additional families narrowed the ca ndidate region, supported locus homogeneity, and did not detect founde r effects. The OPS locus maps to a 13-cM interval between D11S1298 and D11S971 and most likely lies in a 3-cM region between GSTP1 and D11S1 296. At present, no strong candidate genes colocalize with OPS.