一例年轻的成年发病型糖尿病13型患者临床及分子遗传学分析

Clinical and molecular genetic analysis of a patient with maturity onset diabetes of the young type 13: a case report

研究1例KCNJ11基因杂合突变所致年轻的成年发病型糖尿病13(MODY13)家系的临床和分子遗传学特点。该家系先证者为13岁男性患儿,BMI 17.4 kg/m2,体态、发育正常。因“口渴、多饮、多尿1月余,血糖高3 d”收入院,诊断为糖尿病。先证者直系亲属中有三代糖尿病家族史,家系中其他糖尿病患者发病年龄为20~40岁。主要依靠生活方式干预及口服降糖药治疗。家族成员糖尿病病程最长20年,目前无明显糖尿病并发症。对先证者采用目标序列捕获芯片联合高通量DNA测序对43个已知单基因糖尿病相关基因进行捕获测序,对获选的变异位点利用Sanger测序验证,并对其家系成员进行获选变异位点的Sanger测序验证。先证者及其父亲携带KCNJ11(NM⁃000525)基因c.679G>A(p.E227K)位点杂合突变,其母并未携带该基因。先证者祖母及叔父虽未进行基因检测,口服降糖药物治疗有效,且无糖尿病并发症,提示该家系符合常染色体显性遗传模式。MODY13型是一类以常染色体显性模式遗传的单基因疾病,临床上对于儿童和年轻发病且家族遗传背景较强的糖尿病患者,需注意筛查MODY13。

To investigate the characteristics of clinical and molecular genetics in a pedigree with ma⁃turity onset diabetes of the young(MODY)type 13 caused by a heterozygous mutation in KCNJ11 gene.The proband of the family was a male child(13 years old).His BMI was 17.4 kg/m2,with a normal body shape and development.He presented with thirst,polydipsia and polyuria for more than one month,and hy⁃perglycemia for 3 days.He was diagnosed as diabetes mellitus.There are three generations of diabetes family history in the proband’s immediate family.The immediate family members were diagnosed with diabetes between 20~40 years old,and most of them were treated with lifestyle intervention or oral hypoglycemic medications.The longest diabetes duration in the family was 20 years and no obvious diabetic complications occurred.The target sequence capture chip and high⁃throughput DNA sequencing methods were used to cap⁃ture and sequence 43 related genes of the known mono⁃genetic diabetes in the proband.The selected muta⁃tion loci from the proband and his family members were verified by Sanger sequencing method.The proband and his father carried the heterozygous mutation of KCNJ11(NM⁃000525)gene c.679G>A(p.E227K),while his mother did not.Although the proband’s grandmother and uncles did not undergo genetic testing,they responded well in oral hypoglycemic medication therapy and without no diabetic complications.So it suggested an autosomal dominant genetic inheritance pattern.MODY13 is a type of autosomal dominant monogenetic disease.In clinical practice,it is necessary to screen MODY13 in children and young patients with diabetes with strong family genetic background.