表现为妊娠期高血糖的胰十二指肠同源盒1基因突变家系的临床及遗传学研究  

Clinical and genetic study of a Chinese pedigree of pancreatic duodenal homologous box 1 gene mutation with hyperglycemia in pregnancy

作　　者：邓明群 肖新华 宋英娜[2] 李晓青[3] 平凡 Deng Mingqun;Xiao Xinhua;Song Yingna;Li Xiaoqing;Ping Fan(Department of Endocrinology,Key Laboratory of Endocrinology,Ministry of Health,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Beijing 100730,China;Department of Gynaecology and Obstetrics,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Beijing 100730,China;Department of Gastroenterology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医院内分泌科国家卫生健康委员会内分泌重点实验室,100730 [2]中国医学科学院北京协和医院妇产科,100730 [3]中国医学科学院北京协和医院消化内科,100730

出　　处：《中华糖尿病杂志》2020年第1期48-52,共5页CHINESE JOURNAL OF DIABETES MELLITUS

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。Objective 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 ofβ-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.

关 键 词：糖尿病 妊娠 胰十二指肠同源盒1 青少年的成人起病型糖尿病 

分 类 号：R714[医药卫生—妇产科学]