Rong Ju, Li Qiuxia, Zhang Pingping, Wu Xinyu, Huang Jinxian, Li Chao, Liao Zetao, Xie Yingying, Lv Qing, Wei Qiujing, Li Tianwang, Huang Jianlin, Cao Shuangyan, Shen Yan, Gu Jieruo
Division of Rheumatology, the Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road 600, Guangzhou 510630, China.
The Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College and Chinese National Human Genome Research Center, Beijing, China.
PLoS One. 2015 May 15;10(5):e0126348. doi: 10.1371/journal.pone.0126348. eCollection 2015.
Ankylosing spondylitis (AS; MIM 106300) is a common rheumatic disease with strong genetic components affecting approximately 0.3% of the population. The exact genetic mechanism of AS remains elusive. Our previous study showed that AS could be transmitted in an autosomal dominant inheritance mode and a 6-cM candidate region located on the chromosome 2q36.1-36.3 was mapped in a Chinese family. Mutation screening was conducted within the candidate region in the family and other AS by sequencing, and the novel mutation will be further validated in other AS families, sporadic cases and healthy controls by mass spectrometry. We identified a rare non-synonymous mutation (Arg580Gly) in insulin receptor substrate 1 (IRS1) co-segregated with disease phenotype in patients of the family, which was not found in other AS families, sporadic patients and healthy controls. In the study, we found a rare non-synonymous mutation in IRS1 co-segregation in one Chinese family with AS, which indicated a new candidate disease causative gene for AS.
强直性脊柱炎（AS；MIM 106300）是一种常见的风湿性疾病，具有很强的遗传因素，影响着约0.3%的人口。AS的确切遗传机制仍不清楚。我们之前的研究表明，AS可能以常染色体显性遗传模式传递，并且在一个中国家庭中定位了位于2号染色体2q36.1 - 36.3上的一个6厘摩候选区域。通过测序在该家庭及其他AS患者的候选区域内进行突变筛查，新发现的突变将通过质谱法在其他AS家庭、散发病例和健康对照中进一步验证。我们在胰岛素受体底物1（IRS1）中鉴定出一个罕见的非同义突变（Arg580Gly），该突变在该家庭患者中与疾病表型共分离，而在其他AS家庭、散发病例和健康对照中未发现。在本研究中，我们在一个患AS的中国家庭中发现IRS1存在罕见的非同义突变共分离现象，这表明IRS1是AS一个新的候选致病基因。
