目的·研究一个X连锁迟发性脊椎骨骺发育不良（spondyloepiphyseal dysplasia tarda，SEDT）家系的致病基因及突变类型。方法·提取一个SEDT家系6名成员外周血基因组DNA。应用Clearseq遗传性疾病试剂盒靶向捕获先证者基因组样本中与罕见遗传性疾病相关的致病区域，并进行高通量测序，过滤去除高频突变。采用外显子组隐马尔科夫模型（exome hidden Markov model，XHMM）分析拷贝数变异（copy number variant，CNV），并进一步对6名家系成员基因缺失片段的拷贝数进行实时定量PCR分析。结果·高通量测序分析结果显示，先证者X染色体存在2.5 kb缺失（chrX：13 732 385~13 734 927），该区域覆盖转运蛋白复合体亚单位2（transport protein particle complex subunit 2，TRAPPC2）基因的第4~6个外显子。定量PCR结果证实先证者及其表哥均存在该缺失，先证者母亲为杂合缺失，先证者父亲、姐姐和表型正常的舅舅拷贝数均正常。结论·TRAPPC2基因第4~6个外显子片段的缺失为SEDT的致病性突变；同时高通量测序分析中运用XHMM算法可检测到致病基因多个外显子的缺失。

Objective ·To explore the pathogenic gene and the mutation type of a family with X-linked spondyloepiphyseal dysplasia tarda (SEDT). Methods ·Genomic DNA was extracted from the peripheral blood of 6 members of a SEDT family. Clearseq hereditary disease kit was applied to target pathogenic regions related to the rare hereditary diseases in the genomic sample of the proband, and then high-throughput sequencing and deletion of high-frequency variants were preformed. Copy number variant (CNV) was analyzed by using exome-hidden Markov model (XHMM). Real-time quantitative PCR was performed to further analyze the copy numbers of the gene deletion fragment in the 6 family members. Results ·High-throughput sequencing results showed that 2.5 kb fragment deletion existed in the chromosome X (chrX: 13 732 385?13 734 927) of the proband, which covered exon 4?6 of the transport protein particle complex subunit 2 (TRAPPC2) gene. The quantitative PCR results confirmed the proband and his male cousin carried the deficiency. The proband′s mother had a heterozygous deficiency, and the proband′s father, sister and the uncle with normal phenotypes all had normal copy numbers. Conclusion ·The fragment deletion of exon 4?6 of TRAPPC2 gene is the pathogenic mutation of SEDT, and the XHMM algorithm in high-throughput sequencing analysis can detect the deletion of multiple exons in pathogenic genes.