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目的分析1个符合青少年起病的成人糖尿病5型(MODY5)的早发糖尿病合并多发性肾囊肿家系,探讨其家系MODY5临床表型与肝细胞核因子1β(HNF1β)基因的关系。方法选择发现的1个MODY5患者家系,另选择健康体检者2例作为对照。对MODY5患者进行家系调查,收集家庭成员[包括先证者(Ⅱ4)、引产胎儿(Ⅲ1)、大姐(Ⅱ1)、二姐(Ⅱ2)、三姐(Ⅱ3)、父亲(Ⅰ1)]的疾病史。采集该家系中引产胎儿(Ⅲ1)脾脏,抽取该家系其他健在成员及对照者外周静脉血,提取外周血有核细胞DNA,应用聚合酶链式反应技术对HNF1β基因进行扩增及测序分析。结果先证者(Ⅱ4)、先证者父亲(Ⅰ1)、三姐(Ⅱ3)均为早发糖尿病合并多发性肾囊肿,先证者大姐(Ⅱ1)为多发性肾囊肿,二姐(Ⅱ2)仅有糖尿病一种表型。基因测序发现先证者大姐(Ⅱ1)的HNF1β基因第9外显子1968A>G、2142T>A、2312A>C编码区发生突变,家系其他成员及对照者未发现外显子编码区HNF1β基因突变。结论在该MODY5家系中仅发现1例HNF1β基因突变,MODY5临床表型与HNF1β基因型存在较大的异质性。
Objective To analyze the relationship between MODY5 clinical phenotype and hepatocyte nuclear factor-1β (HNF1β) gene in adolescents with MODY5 and early onset diabetes mellitus complicated with multiple renal cyst. Methods A family of MODY5 patients was selected. Two healthy subjects were selected as controls. A pediatric investigation of MODY5 patients was performed to collect the family history of the disease (including the proband (Ⅱ 4), fetus (Ⅲ 1), elder sister (Ⅱ 1), sister (Ⅱ 2), third sister (Ⅱ 3), father (I 1) . The spleen of the induced fetus (Ⅲ 1) in the pedigree was collected and the peripheral venous blood of other healthy individuals and controls in the pedigree were collected. The DNA of peripheral blood was extracted and the HNF1β gene was amplified and sequenced by polymerase chain reaction. Results The proband (Ⅱ 4), the proband’s father (Ⅰ 1) and the third sister (Ⅱ 3) were both early-onset diabetes mellitus complicated with multiple renal cysts, proband S Ⅱ (Ⅱ 1) Only a phenotype of diabetes. Gene sequencing found that mutations in the 1968A> G, 2142T> A and 2312A> C coding regions of exon 9 of HNF1β gene in the eldest sister (Ⅱ 1) of the proband were found. Other members of the pedigree and control did not find HNF1β mutation in exon coding region . Conclusion Only one case of HNF1β gene mutation was found in this MODY5 pedigree. The clinical phenotype of MODY5 was associated with a large heterogeneity of HNF1β genotype.