Targeted exome sequencing identified a novel mutation hotspot and a deletion in Chinese primary hypertrophic osteoarthropathy patients
Targeted exome sequencing identified a novel mutation hotspot and a deletion in Chinese primary hypertrophic osteoarthropathy patients
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DOI：
10.1016/j.cca.2018.10.005
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发表时间：
2018-12-01
影响因子：
5
通讯作者：
Wang, Jian
中科院分区：
文献类型：
--
作者：
Chen, Yulin;Li, Guoqiang;Wang, Jian
背景资料：原发性肥大性骨关节病（PHO）是由基因HPGD和SLCO 2A1突变引起的遗传和临床异质性系统性疾病。本研究的目的是为PHO的早期准确诊断提供有用的信息，并确定中国PHO儿童的致病突变。方法和结果：系统分析了7例中国儿童PHO患者的临床表现、影像学特征。靶向外显子组测序鉴定了先前报道的HPGD基因中的c.310_311delCT突变和新的常见剪接位点突变c.324 + 5G > A。相对定量的真实的时间PCR验证了同一基因中第4号外显子的新型缺失。SLCO2A1基因的突变和结构变异均未检测到。结论：在本研究中，在7例中国儿童患者中发现了纯合子或复合杂合子HPGD突变，表明为常染色体隐性遗传。c.310_311delCT突变和剪接位点突变c.324 + 5G > A可能是中国PHO患者的突变热点。首次报道了HPGD基因的结构变异。在HPGD基因中鉴定的纯合、复合杂合突变或结构变异表明，靶向外显子组测序可能是儿科PHO诊断和突变分析的优选方法。
Background: Primary hypertrophic osteoarthropathy (PHO) is a genetically and clinically heterogeneous systematic disorder caused by mutations in genes HPGD and SLCO2A1. The purpose of the present study is to provide useful information for the early and precise diagnosis of PHO and identify causative mutations in Chinese PHO children.Methods and results: The clinical manifestations, radiographic features of seven Chinese pediatric patients were systematically analyzed. Targeted exome sequencing identified a previously reported c.310_311delCT mutation and a novel common splicing site mutation c.324 + 5G > A in the HPGD gene. Relative quantitative real time PCR validated a novel deletion of the exon 4 in the same gene. Neither mutations nor structural variations in the gene SLCO2A1 were detected.Conclusions: In the present study, homozygous or compound heterozygous HPGD mutations were identified in seven Chinese pediatric patients, suggesting an autosomal recessive inheritance. The c.310_311delCT mutation and the splicing site mutation c.324 + 5G > A were likely to be mutational hotspots in Chinese PHO patients. For the first time, a structural variation of the HPGD gene was reported. Homozygous, compound heterozygous mutations or structural variation identified in the HPGD gene proposed that targeted exome sequencing may be a preferable method for pediatric PHO diagnosis and mutation analysis.