Adolescent Idiopathic Scoliosis Gene Identified

The condition, adolescent idiopathic scoliosis (AIS), is a type of scoliosis afflicting patients between 10 and 18 years of age, and is the most common type of pediatric skeletal disease in which the specific cause is not known. Therefore it is termed “idiopathic,” meaning is arises spontaneously from an obscure or unknown cause.

However, many clinical and genetic studies suggest a contribution of genetic factors as approximately 30 percent of AIS patients have some family history of scoliosis. AIS affects about two percent of school-age children, and primarily in those of Asian or Caucasian decent.

Scoliosis is a medical condition in which a person’s spine is curved from side to side in a complex three-dimensional deformity, which exceeds more than 10 degrees when viewed from the coronal plane or sagittal plane. On isolated imaging the spine of a scoliosis patient may look like an “S” or a “C”, rather than a straight line.

Scoliosis is classified as either congenital – caused by vertebral anomalies present at birth, idiopathic – cause unknown, or is secondary to another primary condition. Secondary scoliosis may be the result of any number of neuromuscular conditions like spina bifida, cerebral palsy, or physical trauma.

An estimated 65 percent of scoliosis cases are idiopathic, about 15 percent are congenital, and about 10 percent are secondary to a neuromuscular disease.

The onset of adolescent idiopathic scoliosis generally does not result in immediate discomfort or neurologic symptoms. The curve of the spine does not put pressure on organs nor is there a noticeable shortness of breath seen with AIS, according to the Scoliosis Research Society (SRS).

When scoliosis begins in adolescent patients, often there is some lower back pain. However, lower back pain is not uncommon as many teens participate in a large number of activities without having good core abdominal and back strength or flexibility. Therefore, the condition is diagnosed by a doctor using tactile and imaging tests.

To correct the curvature, treatments include physical therapy, casting, bracing, and surgery – anterior and posterior fusion.

Research has been ongoing to identify the cause of AIS, including genetic factors. Thus far there are no identifiable causes for this condition, but researchers from the RIKEN Center for Integrative Medical Sciences in Japan believes they’ve isolated the first gene to be associated with AIS.

In the study, published in the journal Nature Genetics, doctors Ikuyo Kou and Shiro Ikegawa, and their team wanted to identify the genes associated with a susceptibility of acquiring the condition, in hopes of understanding the causes and development of scoliosis.

The genome of 1,819 Japanese individuals afflicted with scoliosis were compared it to 25,939 other Japanese individuals. This process allowed the team to identify a gene associated with a susceptibility to develop scoliosis on chromosome 6, GPR126. The association was replicated in Han Chinese and Caucasian populations.

Probable G-protein coupled receptor 126 is a protein that in humans is encoded by the GPR126 gene. This gene encodes a member of the adhesion-GPCR receptor family, characterized by an extended extracellular region with a variable number of N-terminal protein modules coupled to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain. It is involved in the process of myelination.

It has also been found that variations in this gene can affect a person’s stature as the gene is involved in the growth and development of the spine during childhood. GPR126 is highly expressed in cartilage and that suppression of this gene leads to delayed growth and bone tissue formation in the developing spine. GPR126 is also plays a role in human height and trunk length.

The researchers concluded, further studies will be necessary to properly elucidate how alterations in the GPR126 amplifies the risk of AIS.

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