摘要目的 确定一个X连锁迟发性脊椎骨骺发育不良(X-linked spondyloepiphyseal dysplasia tarda,X-SEDL)家系TRAPPC2基因的突变类型,并探讨该家系发病的分子遗传学机制.方法 采集该家系32名成员及50名正常成年人对照者的外周血样,提取基因组DNA.采用聚合酶链反应扩增TRAPPC2基因第3～6外显子及侧翼区,对扩增产物进行双向直接测序,将测序结果与GenBank中的TRAPPC2的参考序列进行比对,以确定突变位点及类型.结果 在先证者TRAPPC2基因第3内含子剪接供体处发现一个c.93+5G＞A突变,TRAPPC2基因第3～6外显子的核苷酸序列未见改变.该家系成员中,6例男性患者、8例女性携带者均检出同一突变,在其余表型正常的18名成员及正常对照者中未发现该突变.结论 在中国的X-SEDL患者中发现了TRAPPC2基因的c.93+5G＞A突变,丰富了TRAPPC2基因的突变谱.上述检测将有助于对X-SEDL进行症状前诊断及产前诊断.

abstractsObjective To identify potential mutation of TRAPPC2 gene in a Chinese family affected with X-linked spondyloepiphyseal dysplasia tarda (X-SEDL),and explore its underlying molecular mechanism.Methods Peripheral blood samples were collected from 32 members of the family and 50 healthy adults to extract genomic DNA.DNA sequences of exons 3 to 6 and their exon/intron boundaries were amplified with PCR amplification.Direct bi-directional sequencing analysis was performed on the PCR products.The sequences were aligned to the reference sequences from the GenBank to determine mutation site and type.Results A nucleotide substitution of the splice-donor in TRAPPC2 intron 3,c.93+5G＞A,was detected in the proband,but no sequence change was detected in TRAPPC2 exons 3 to 6.All of the 6 male patients and 8 female carriers from the family were detected to have carried this mutation.The same mutation was not found in the remaining 18 family members with a normal phenotype and 50 healthy controls.Conclusion We have detected a c.93+5G＞A mutation in the TRAPPC2 gene in a Chinese family affected with X-SEDL.Our results have expanded the spectrum of TRAPPC2 mutations and is helpful for presymptomatic and prenatal diagnoses of this disease.