摘要目的:探讨一个以妊娠期高血糖为主要表现的胰十二指肠同源盒1（PDX1）基因突变家系的临床表现及分子遗传学机制。方法:回顾性研究一个孕期发现的高血糖家系，其先证者表现为妊娠期高血糖且营养不良，进行单基因糖尿病目标基因二代测序捕获和一代测序验证，比对遗传学数据库，分析突变位点的人群突变频率及物种保守性，并采用Mutation Taster、Polyphen-2、FATHMM等软件进行生物信息学分析，根据美国医学遗传学与基因组学学会分级进行致病性判定，根据基因检测结果对患者的诊治方案进行调整，并回顾文献中PDX1基因突变在妊娠期高血糖中的研究。结果:基因检测提示PDX1基因突变（p.D64E），该突变位点物种保守性高，家系验证提示PDX1基因突变与糖尿病表型共分离，是新发现的位点。先证者除β细胞功能缺陷之外，还合并胰腺外分泌功能障碍，进行胰岛素及胰酶补充治疗后患者孕重增加满意，生化指标恢复正常。回顾文献发现，PDX1基因突变在高加索人种中可导致妊娠期高血糖及围产期不良结局。结论:本研究发现在中国人群中反复出现的妊娠期高血糖可由PDX1基因突变导致，提示对该类患者应进行胰腺外分泌功能检测，如有异常应及时进行功能替代，进而实现精准诊疗。同时提示在妊娠期高血糖人群中建立单基因糖尿病筛查的重要性。

abstractsObjective:To retrospectively study the clinical manifestations and molecular genetics of a pedigree of pancreatic duodenal homeobox 1 (PDX1) gene mutation with hyperglycemia in pregnancy.Methods:We reported a family with hyperglycemia discovered during pregnancy. The proband showed hyperglycemia and malnutrition during pregnancy. The next generation sequencing of target genes of monogenic diabetes was performed and then Sanger sequencing to verify the suspected gene. Frequency and species conservation of the mutation site was analyzed. Mutation Taster, Polyphen-2, FATHMM and other software was performed for bioinfor matics analysis. Classification for pathogenicity was determined according to the American Society of Medical Genetics and Genomics. Treatment strategy was adjusted for the proband according to the gene result. We reviewed the literature of PDX1 gene mutation in hyperglycemia during pregnancy.Results:A PDX1 gene mutation (p.D64E) was detected in the proband. It is a novel mutation and highly conserved in species. The mutation was co-segregated with the clinical phenotypes of diabetes within the pedigrees. In addition to the defects of β-cell function, the proband also suffered from pancreatic exocrine dysfunction. After insulin and trypsin supplementation, her weight increased and the biochemical indicators returned to normal. It is reported in the literature that PDX1 gene mutations in the Caucasian population can lead to hyperglycemia during pregnancy and poor perinatal outcomes.Conclusion:Our study firstly indicated that mutations in the PDX1 gene could result in hyperglycemia during pregnancy in Chinese population, suggesting that pancreatic exocrine function should be evaluated in these patients. Trypsin replacement should be prescribed in time to achieve precision therapy. Meanwhile, this study also suggests the importance of establishing screening methods for monogenetic diabetes in hyperglycemic patients during pregnancy.