摘要目的 对1例迟发性脊柱骨骺发育不良(X-linked spondyloepiphyseal dysplasia tarda,SEDT)家系进行TRAPPC2基因突变分析,并为其提供遗传咨询和产前诊断.方法 采用聚合酶链反应和DNA直接测序法对先证者及其父亲TRAPPC2基因的4个外显子与侧翼区进行序列分析.为先证者于孕18周时行羊膜腔穿刺术,提取胎儿羊水细胞基因组DNA,应用SRY基因对胎儿进行性别鉴定,同时对TRAPPC2基因进行序列分析.结果 测序发现先证者父亲TRAPPC2基因第4外显子存在c.209G＞A位点突变,先证者cDNA第209位碱基存在G＞A杂合突变,上述突变为无义突变,可导致蛋白翻译提前终止.在正常对照中未发现相同的突变.应用SRY基因对胎儿进行性别鉴定结果为阳性.对胎儿TRAPPC2基因序列分析发现其第4外显子亦存在c.209G＞A位点突变.结论 TRAPPC2基因第4外显子c.209G＞A位点突变是该家系中3例男性患者的主要病因.先证者是致病突变的携带者,胎儿为男性并携带与先证者相同的突变,因此具有较高的患病风险,建议患者应及早终止妊娠.产前基因诊断是预防和控制该类疾病的有效手段.

abstractsObjective To analyze TRAPPC2 gene mutation in a family with X-linked spondyloepiphyseal dysplasia tarda and to provide genetic counseling and prenatal diagnosis.Methods All of 4 exons of the TRAPPC2 gene and their flanking sequences in the proband and her father were analyzed with polymerase chain reaction and direct DNA sequencing.Genomic DNA of the proband's fetus was extracted from amniotic fluid sampled at 18th gestational week.Gender of the fetus was determined by the presence of SRY gene.The sequence of fetal TRAPPC2 gene was also analyzed.Results A c.209G＞A mutation was identified in exon 4 of the TRAPPC2 gene in the proband and her father.The fetus of was determined to be a male and also have carried the c.209G＞A mutation.Conclusion A c.209G＞A mutation of TRAPPC2 exon 4 probably underlies clinical manifestations in this family.The proband is a carrier,and her fetus is a male carrying the same mutation.Prenatal diagnosis is an effective method for the prevention of the disease.