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Gene identified, responsible for a spectrum of disorders affecting the bones and connective tissue

2013-05-09
(Press-News.org) Researchers from the RIKEN Center for Integrative Medical Sciences have identified a gene that when mutated is responsible for a spectrum of disorders affecting the bones and connective tissue. This finding opens new avenues for research into a diagnosis and treatment for these until now incurable diseases.

The study is published today in the American Journal of Human Genetics.

Spondyloepimetaphyseal dysplasia with joint laxity, type I or SEMD-JL1 is a disorder of the skeleton resulting in short stature and spinal problems starting from birth, and worsening with age. The disease is also known as SEMD Beighton type.

In order to find the gene responsible for the disorder, and Dr Ikegawa and his team examined the entire coding sequence of the genome of 7 individuals suffering from SEMD-JL1 using next-generation sequencing technology.

The researchers found that the study subjects all had mutations that resulted in significant loss of function of the gene B3GALT6, known to be involved in the biosynthesis of an important component of connective tissue.

To the reseachers' surprise, mutations in B3GALT6 were also found in patients suffering from a disorder of the connective tissue called Ehlers-Danlos syndrome progeroid type. The researchers show that a deficiency in the B3GALT6 enzyme results in a spectrum of disorders affecting various tissues, including the skin, bones, cartilage, tendons and ligaments. Their results indicate that B3GALT6 is essential for the development and the maintenance of these tissues.

B3GALT6 is known to encode for an enzyme involved in the biosynthesis of the glucosaminoglycan (GAG) linker region.

"The GAG linker region is key for GAG biosynthesis and proteoglycan metabolism," explains Dr Ikegawa "and proteoglycans are important because they are a major component of the matrix of connective tissue in animals."

"Our findings show that mutations in B3GALT6 cause a spectrum of disorders that were previously thought to belong to different families of diseases – some were thought to be skeletal dysplasia and others connective tissue disorders," explain the authors.

"More clinical, genetic and biological studies are needed to understand the pathological mechanism of the diseases and the role of GAG metabolism and function," they conclude.



INFORMATION:

For more information please contact:

Juliette Savin
Global Relations Office
RIKEN
Tel: +81-(0)48-462-1225 / Fax: +81-(0)48-463-3687
email: pr@riken.jp

A picture and a copy of the paper are available on request.

Picture caption: Representative clinical pictures and X-ray for spondyloepimetaphyseal dysplasia with joint laxity, type 1 (SEMD-JL1) and Ehlers-Danlos syndrome, progeroid type with B3GALT6 mutations.

Reference

"Mutations in B3GALT6 which Encodes a Glycosaminoglycan Linker Region Enzyme Cause a Spectrum of Skeletal and Connective Tissue Disorders." Nakajima et al. American Journal of Human Genetics 2013, DOI:

About RIKEN

RIKEN is Japan's flagship research institute devoted to basic and applied research. Over 2500 papers by RIKEN researchers are published every year in reputable scientific and technical journals, covering topics ranging across a broad spectrum of disciplines including physics, chemistry, biology, medical science and engineering. RIKEN's advanced research environment and strong emphasis on interdisciplinary collaboration has earned itself an unparalleled reputation for scientific excellence in Japan and around the world.

About the Center for Integrative Medical Sciences

The Center for Integrative Medical Sciences, based in Yokohama, aims to develop revolutionary medical therapies based on collaborative projects between researchers from different areas of science. By achieving a deeper understanding of homeostasis, and how the breakdown of homeostasis leads to disease, scientists at IMS are working to develop personalized preventive medicine and personalized medicine that can allow us to lead healthier lives. The centers focuses include genomics, immunology, allergies, inflammation, endocrinology, and the new field of metabolomics.



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[Press-News.org] Gene identified, responsible for a spectrum of disorders affecting the bones and connective tissue