Changlong Guo1, Xin Tian1, Feifei Han1, Lihong Liu1, Jianen Gao1, Xu Ma1. 1. From the National Research Institute for Family Planning, Beijing; The No. 1 Hospital of Shijiazhuang, Shijiazhuang; Shijiazhuang Maternity Hospital, Shijiazhuang; and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China. Supported by grants 0102012DFB30130 from the International Science & Technology Cooperation Program of China; 2016YFC1000300, 20161000307, 2016YFC1000803, and 2017YFC1002000 from the National Key Research and Development Program; and 81501418 from the National Natural Science Fund. C. Guo, MD, PhD, National Research Institute for Family Planning; X. Tian, BS, The No. 1 Hospital of Shijiazhuang, Shijiazhuang Maternity Hospital; F. Han, MD, PhD, Beijing Chao-Yang Hospital, Capital Medical University; L. Liu, MD, PhD, Beijing Chao-Yang Hospital, Capital Medical University; J. Gao, MD, PhD, National Research Institute for Family Planning; X. Ma, MD, PhD, National Research Institute for Family Planning. Dr. Guo and Xin Tian contributed equally to this report. Address correspondence to Prof. J. Gao, Center for Genetics, National Research Institute for Family Planning, 12 Dahuisi Road, Haidian, Beijing, 100081, China. E-mail: gaojianen@nrifp.org.cn. Accepted for publication September 27, 2019.
Abstract
OBJECTIVE: SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome is a type of rare chronic aseptic inflammation of unknown etiology. To date, no research to our knowledge has reported copy number variation (CNV) of genes that could affect predisposition to SAPHO syndrome. We investigated the association between CNV profile and SAPHO syndrome. METHODS: We used array comparative genomic hybridization (CGH) to screen for CNV in a nuclear family including 2 patients and a healthy control. We then validated the copy numbers of candidate genes found in the array CGH assay and other candidate genes by TaqMan real-time PCR in 360 case and control samples. RESULTS: Ten regions from 8 chromosomes were found to have abnormal gene copies in the nuclear family, so the CNV of candidate genes (ADAM5, CSF2RA, IL3RA, and 9 other genes) were tested by TaqMan PCR. Significant copy number loss of CSF2RA (p = 0.000) and NOD2 (p = 0.005), and significant copy number gain of MEGF6 (p = 0.002) and ADAM5 (p = 0.000) were seen in patients with SAPHO compared with controls at the a = 0.05 level. There were no differences in the other 8 candidate genes between patient and control samples (p > 0.05). CONCLUSION: Our study established the first association between CNV in CSF2RA, NOD2, MEGF6, and ADAM5 and SAPHO syndrome. These findings may offer insight into the pathogenesis of SAPHO and provide the basis for improved diagnosis and treatment.
OBJECTIVE: SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome is a type of rare chronic aseptic inflammation of unknown etiology. To date, no research to our knowledge has reported copy number variation (CNV) of genes that could affect predisposition to SAPHO syndrome. We investigated the association between CNV profile and SAPHO syndrome. METHODS: We used array comparative genomic hybridization (CGH) to screen for CNV in a nuclear family including 2 patients and a healthy control. We then validated the copy numbers of candidate genes found in the array CGH assay and other candidate genes by TaqMan real-time PCR in 360 case and control samples. RESULTS: Ten regions from 8 chromosomes were found to have abnormal gene copies in the nuclear family, so the CNV of candidate genes (ADAM5, CSF2RA, IL3RA, and 9 other genes) were tested by TaqMan PCR. Significant copy number loss of CSF2RA (p = 0.000) and NOD2 (p = 0.005), and significant copy number gain of MEGF6 (p = 0.002) and ADAM5 (p = 0.000) were seen in patients with SAPHO compared with controls at the a = 0.05 level. There were no differences in the other 8 candidate genes between patient and control samples (p > 0.05). CONCLUSION: Our study established the first association between CNV in CSF2RA, NOD2, MEGF6, and ADAM5 and SAPHO syndrome. These findings may offer insight into the pathogenesis of SAPHO and provide the basis for improved diagnosis and treatment.