Potent gene screening strategy based on family-based patients with lumbar discherniation / 西安交通大学学报(医学版)

ABSTRACT

Objective: To look for a potent gene that may cause intervertebral disc degeneration in a family with intervertebral disc herniation by exome sequencing four patients with intervertebral disc herniation so as to provide possible help for studies on the causes and mechanisms of intervertebral disc diseases. Methods: We collected the serum of patients with lumbar disc herniation treated at The First Affiliated Hospital of Xi'an Jiaotong University, The First Affiliated Hospital of Xi'an Medical College, and Xi'an Tangcheng Hospital from January 2010 to December 2016. A detailed medical history was collected and family survey was conducted to find a family with high incidence of degenerative intervertebral disc disease. Then we found 4 patients aged 20 to 50 years with lumbar disc herniation in this family. Exome sequencing was used to analyze the common exon mutation sites of the 4 patients to find the common mutation sites. Results: The common mutation IGFBP6, Chr12g.53494591T>C, was detected in the 4 samples. The Sanger sequencing performed in-family validation revealed that the IGFBP6 showed a C/T type in all the four patients and a T type in all the five normal controls. Finally, verification was performed in 200 normal controls and no mutation was found in this site. Therefore, the IGFBP6 might be the effector gene that caused intervertebral disc degeneration in this family. Conclusion: The mutation site of IGFBP6, c.T430C (p.S144P) (Chr12g.53494591T>C), may be a factor that contributes to the high incidence of intervertebral disc herniation in this family. We still need to verify the function of the gene in future. Our study has also confirmed that exome sequencing technology can be applied to the detection of disease-causing genes in complex diseases.