摘要：目的 探讨 １ 例骨硬化症患儿的临床特点及遗传学病因，提高临床医师对遗传性恶性骨硬化症的认识。 方法 收集患 儿及父母的外周血标本进行生化指标检测及基因组 ＤＮＡ 抽提；应用全外显子组高通量测序技术进行基因检测，Ｓａｎｇｅｒ 测序进 一步验证突变位点，并对数据进行分析；结合患儿病史及体征，分析其临床病理参数。 结果 全外显子组测序结合 Ｓａｎｇｅｒ 测 序验证发现患儿 ＴＣＩＲＧ１ 基因在 ５ 号外显子 Ｃ４９３＿Ｔ４９４ 存在 ＣＴ 二核苷酸纯合性插入，该 ＣＴ 二核苷酸插入导致 ＴＣＩＲＧ１ 发生 移码突变。 根据美国医学遗传学与基因组学学会（ＡＣＭＧ）及变异位点检测系统推测 ＴＣＩＲＧ１ 基因的 ｃ．４９３＿４９４ｄｕｐ 突变为致 病突变，与常染色体隐性遗传疾病骨硬化症Ⅰ型（ ｏｓｔｅｏｐｅｔｒｏｓｉｓ，ａｕｔｏｓｏｍａｌ ｒｅｃｅｓｓｉｖｅ Ⅰ）相关。 结论 先证者 ＴＣＩＲＧ１ 基因的外 显子发生变异，导致其患骨硬化症Ⅰ型常染色体隐性遗传疾病，该突变 ｃ．４９３＿４９４ｄｕｐ 是一种新型突变，患者突变位点的确认 有助于患儿的疾病诊断及父母再生育指导。
Abstract: Objective The clinical characteristics and genetic etiology of children in a family with osteosclerosis were analyzed by genetie testing to improve the understanding of clinicians on hereditary malignant osteosclerosis. Methods The biochemical indexes and genes of the children in the family were detected, combined with the medical history of the children, and the clinical symptoms of the disease were summarized. Genonic DNA from peripheral blood of the children and their parents was extracted, and the whole-exome high-throughput sequencing was used for gene detection. Sanger sequencing was used to further verify the mutation sites, and the data were analyzed. Results Whole exome sequencing combined with Sanger sequencing venified that the homozygous CT dinucleotide insertion of TCIRGI in exon 5 C493. _T494, which is resulted in the code shift mutation of TCIRGI. According to the recommendations of the American Society of Medical Genetics and Genomics ( ACMG) guidelines and the ClinGen Group of Experts on the application of the guidelines ,it was suggested that the C.493_ 494DUP mutation of TCIRGI was a pathogenie mutation, which is related to the autosomal recessive genetic disease Osteopetrosis, autosomal recessive I . Conclusion The exon of the TCIRG1 gene has been mutated ，leading to the risk of bone sclerosis typeI autosomal recessive genetic disease，the mutation c.493_ 494dup is a new type of mutation.The dentification of mutations is helpful to the diagnosis of the disease of the child and the prenatal diagnosis of the parents when they give birth again, which is conducive to healthy birth and good care, improve the family happiness and reduce the social burden.