Identification of a gene mutated in a hereditary form of rickets

As a team of scientists led by the human geneticist Tim Strom reports in the November issue of Nature Genetics, mutations were identified in the DMP1 gene, which is responsible for the production of dentin matrix protein 1. The protein is mainly expressed in the bone matrix. If mutated, phosphate is lost via the kidney resulting in hypophosphatemia and rickets. “Since rickets due to vitamin D deficiency has become rare in children because of vitamin D supplementation, a large proportion of the cases with rickets are nowadays caused by hypophosphatemia,” Dr. Strom explained. Both phosphate and calcium are minerals, which we take up with our daily diet and which are necessary for bone mineralization.

Deficiency of these minerals leads to rickets characterized by softening of the bones resulting in bowleg or knock-knee. The scientists have been investigating the genetic defects leading to hypophosphatemic rickets for several years and have found mutations in different genes. DMP1 mutations were now identified by studying a family suggesting autosomal recessive inheritance, while the known gene defects are inherited in an autosomal dominant or X-linked mode.

“Since mutations in several genes lead to hypophosphatemia, we assume that there is a metabolic pathway which is responsible for the regulation of phosphate homeostasis and which the mutations interfere with. Further research will show how the bone is linked with renal phosphate reabsorption,“ said Dr. Strom, „and once the molecular processes are elucidated, new therapeutic possibilities may open up.“