Whole exome sequencing implicates PTCH1 and COL17A1 genes in ossification of the posterior longitudinal ligament of the cervical spine in Chinese patients
Whole exome sequencing implicates PTCH1 and COL17A1 genes in ossification of the posterior longitudinal ligament of the cervical spine in Chinese patients
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DOI：
10.4238/2014.march.17.7
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发表时间：
2014-01-01
影响因子：
0.4
通讯作者：
Zhang, X. N.
中科院分区：
文献类型：
--
作者：
Wei, W.;He, H. -L.;Zhang, X. N.
颈椎后纵韧带骨化(OPLL)是一种复杂的多因素疾病。OPLL患者通常在40多岁或50多岁时出现症状。OPLL的遗传学基础仍然知之甚少。外显子组捕获结合大规模并行DNA测序已被认为是寻找单基因和多基因疾病致病基因的一种有效策略。为了确定与OPLL相关的候选致病基因，我们对两例无血缘关系的华南OPLL患者进行了全外显子测序。通过聚合酶链式反应扩增出候选基因的全部DNA编码区，并对其进行Sanger测序。对常见的单核苷酸多态进行关联分析。Wes在两例混合性OPLL女性患者中发现了p.T265S/ptch1、p.P1232L/ptch1和p.T902S/COL17A1突变。Sanger测序证实了这一点。P1232L/ptch1、N1374D/COL17A1和T902S/COL17A1在3例男性持续性OPLL和1例女性混合性OPLL中被鉴定。相关研究表明，COL17A1中的rs805698和rs4918079 SNPs与OPLL显著相关。这项研究表明，WES可能是揭示OPLL显著遗传参与的一种实用方法。Ptch1和COL17A1基因突变可能与OPLL的发生有关。
Ossification of the posterior longitudinal ligament (OPLL) of the cervical spine is a complex multifactorial disease. Patients with OPLL commonly present with symptoms in their 40s or 50s. The genetic basis of OPLL remains poorly understood. Exome capture combined with massively parallel DNA sequencing has been proposed as an efficient strategy to search for disease-causing genes of both monogenic and multigenic disorders. To identify candidate pathogenic genes associated with OPLL, we performed whole exome sequencing (WES) on two unrelated southern Chinese OPLL patients. The entire DNA coding region of the candidate genes was amplified by PCR and Sanger sequenced. The common single nucleotide polymorphisms were analyzed by association studies. WES revealed p. T265S/PTCH1, p. P1232L/PTCH1, and p. T902S/COL17A1 mutants in the two female cases with mixed OPLL. These were confirmed by Sanger sequencing. p. P1232L/PTCH1, p. N1374D/COL17A1 and p. T902S/COL17A1 were subsequently identified in three males with continuous OPLL and one female with mixed OPLL. The association studies indicated that the SNPs rs805698 and rs4918079 in COL17A1 were significantly associated with OPLL. This study suggests that WES may be a practical approach to revealing significant genetic involvement in OPLL. Variants of the PTCH1 and COL17A1 genes may contribute to the development of OPLL.