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

May 9, 2013
This image shows: A and B: 34 year-old man with SEMD-JL1 A: clinical picture. B: Lateral spine X-ray. C: 5 year-old girl with Ehlers-Danlos syndrome. Credit: RIKEN

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 with joint laxity, type I or SEMD-JL1 is a disorder of the skeleton resulting in 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 of an important component of .

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, , 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.

Explore further: Cartilage damaged from exercise may aid in early osteoarthritis detection

More information: "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.

Related Stories

Cartilage damaged from exercise may aid in early osteoarthritis detection

April 2, 2013
Osteoarthritis is the most common joint disorder, affecting about one-third of older adults, and currently there is no cure. A study published by Cell Press April 2nd in the Biophysical Journal reveals how the nanoscale biomechanical ...

Rare mutations may help explain aneurysm in high-risk families

February 3, 2012
An innovative approach to genome screening has provided clues about rare mutations that may make people susceptible to brain aneurysms, predisposing them to brain bleeds, according to preliminary late-breaking research presented ...

Studies in mice confirm that mutations in the gene, UBE3B, cause a rare genetic disorder in children

November 29, 2012
Researchers have defined the gene responsible for a rare developmental disorder in children. The team showed that rare variation in a gene involved in brain development causes the disorder. This is the first time that this ...

Scientists discover gene behind rare disorders

October 9, 2012
Scientists at the Montreal Neurological Institute and Hospital – The Neuro, McGill University working with a team at Oxford University have uncovered the genetic defect underlying a group of rare genetic disorders.

Mystery disease solved by gene experts

May 3, 2013
(Medical Xpress)—A global team of researchers has identified the gene behind an Australian toddler's paediatric brain disorder in a discovery that is paving the way for the diagnosis and treatment of other children with ...

Research identifies gene mutations associated with nearsightedness

May 2, 2013
People have long taken for granted that glasses and contact lenses improve vision for nearsightedness, but the genetic factors behind the common condition have remained blurry. Now researchers at Duke Medicine are closer ...

Recommended for you

Genome analysis with near-complete privacy possible, say researchers

August 17, 2017
It is now possible to scour complete human genomes for the presence of disease-associated genes without revealing any genetic information not directly associated with the inquiry, say Stanford University researchers.

Science Says: DNA test results may not change health habits

August 17, 2017
If you learned your DNA made you more susceptible to getting a disease, wouldn't you work to stay healthy?

Genetic variants found to play key role in human immune system

August 16, 2017
It is widely recognized that people respond differently to infections. This can partially be explained by genetics, shows a new study published today in Nature Communications by an international collaboration of researchers ...

Phenotype varies for presumed pathogenic variants in KCNB1

August 16, 2017
(HealthDay)—De novo KCNB1 missense and loss-of-function variants are associated with neurodevelopmental disorders, with or without seizures, according to a study published online Aug. 14 in JAMA Neurology.

Active non-coding DNA might help pinpoint genetic risk for psychiatric disorders

August 16, 2017
Northwestern Medicine scientists have demonstrated a new method of analyzing non-coding regions of DNA in neurons, which may help to pinpoint which genetic variants are most important to the development of schizophrenia and ...

Evolved masculine and feminine behaviors can be inherited from social environment

August 15, 2017
The different ways men and women behave, passed down from generation to generation, can be inherited from our social environment - not just from genes, experts have suggested.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.