Thus, on the endogamous genetic background of Indian Tamils, SOST1 from sclerostin deficiency compared to SOST2 from LRP4 deactivation is a more severe and life-threatening disorder featuring complications due to osteosclerosis of especially the skull.
Sclerosteosis and Van Buchem disease are two rare bone sclerosing disorders characterized by increased bone mineral density, tall stature and entrapment of cranial nerves due to overgrowth of a highly dense bone.
Individuals who are homozygous for this mutation have sclerosteosis, a disease with no detectable circulating sclerostin, resulting in generalized osteosclerosis with skeletal deformities, cranial nerve compression, and increased intracranial pressure due to boney overgrowth in the skull, and premature death.
The osteoclastogenesis inhibitory factorosteoprotegerin (OPG) seems to be regulated by TGF beta-1 and substantial involvement of OPG expression in the process of osteosclerosis in IMF has recently been suggested.
Gene knockout experiments using such animal models have suggested the essential role of hematopoietic cell-derived transforming growth factor beta1 in inducing bone marrow fibrosis and stromal cell-derived osteoprotegerin in promoting osteosclerosis.
Interleukin-11 as an osteoprotegerin-inducing factor in culture medium of blastic cells from a patient with acute megakaryocytic leukemia complicated with osteosclerosis.
These results suggest that osteosclerosis in IMF may be related to overproduction of OPG and enhanced level of OPG is not due to the effect of TGF-beta1 on the BMS cells.
Interleukin-11 as an osteoprotegerin-inducing factor in culture medium of blastic cells from a patient with acute megakaryocytic leukemia complicated with osteosclerosis.
A novel FAM20C mutation causing hypophosphatemic osteomalacia with osteosclerosis (mild Raine syndrome) in an elderly man with spontaneous osteonecrosis of the knee.
CLC-7 mutations are known to cause autosomal dominant OPT type 2, also called Albers-Schonberg disease, which is characterized by osteosclerosis, predominantly of the spine, pelvis and skull base, resulting in bone fragility and fractures.
Our results demonstrate that mutations in FAM20C provide a putative new mechanism in human subjects leading to dysregulated FGF23 levels, hypophosphatemia, hyperphosphaturia, dental anomalies, intracerebral calcifications and osteosclerosis of the long bones in the absence of rickets.
Raine syndrome is an autosomal recessive disorder caused by mutations in the FAM20C gene that is characterized by generalized osteosclerosis with periosteal new bone formation and distinctive craniofacial dysmorphism.