Discovery: Gene Mutation In Scoliosis

Researchers led by scientists at the Medical Genetics Institute at Cedars-Sinai Medical Center have identified a gene mutation and molecular mechanism causing an inherited form of scoliosis. Mutations in the TRPV4 gene cause a type of brachyolmia, a skeletal dysplasia. Those inheriting the disorder have a shorter-than-average trunk, limbs and fingers and toes, and are affected by scoliosis, primarily in the lumbar vertebrae. Mutations of the TRPV4 gene appear to cause increased calcium in the cells of the developing skeleton. This is the first study to identify this mechanism as a contributor to skeletal dysplasias. The findings suggest that calcium channel balance is important in normal spine development. Also, for skeletal abnormalities caused by TRPV4 gene mutations, the use of calcium channel inhibitors could represent a future approach to treatment.

Researchers led by scientists at the Medical Genetics Institute at Cedars-Sinai Medical Center have identified a gene mutation and molecular mechanism causing an inherited form of scoliosis.

Mutations in the TRPV4 gene cause a type of brachyolmia, a skeletal dysplasia. Those inheriting the disorder have a shorter-than-average trunk, limbs and fingers and toes, and are affected by scoliosis, primarily in the lumbar vertebrae.

Mutations of the TRPV4 gene appear to cause increased calcium in the cells of the developing skeleton. This is the first study to identify this mechanism as a contributor to skeletal dysplasias. The findings suggest that calcium channel balance is important in normal spine development. Also, for skeletal abnormalities caused by TRPV4 gene mutations, the use of calcium channel inhibitors could represent a future approach to treatment.

The research was conducted by a multinational team led by scientists at the Medical Genetics Institute at Cedars-Sinai Medical Center. Daniel H. Cohn, Ph.D., research scientist and co-director of the International Skeletal Dysplasia Registry at Cedars-Sinai, is available to provide detailed information. Cohn is senior and corresponding author of the Nature Genetics article and available for interviews.

The International Skeletal Dysplasia Registry was established at Cedars-Sinai in 1970 by David L. Rimoin, M.D., Ph.D., chairman of the Medical Genetics Institute. Supported by grants from the National Institutes of Health and now documenting more than 15,000 cases, the registry is the largest research program of its kind, tracking the diagnosis, treatment and outcomes of patients with any of the 350 types of skeletal dysplasia.

Citation: Nature Genetics, “Gain-of-function mutations in the gene encoding of calcium-permeable cation channel TRPV4 cause autosomal dominant brachyolmia, available online June 29, 2008.

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