母系遗传伴耳聋糖尿病患者线粒体DNA3243A〉G突变与临床特点之间的关系

Association of clinical features with mitochondriai DNA 3243 A to G mutation heteroplasmy levels in patients with maternally inherited diabetes and deafness

目的对线粒体家系临床特点及基因突变结果进行分析总结，以提高临床对线粒体糖尿病的认识和诊治。方法对北京协和医院2007年至2014年12月间收治的线粒体DNA3243位点A〉G突变导致线粒体糖尿病的6个家系共16例患者的临床特点进行分析总结，通过外周血DNA直接测序（Sanger法）对线粒体DNA3243位点A〉G突变进行鉴定，突变程度用G峰值高度比A峰值高度（G／A）表示。结果早发糖尿病[起病年龄（35．0±14．6）岁]伴耳聋、体型正常或偏瘦、母系遗传倾向者可提示存在线粒体糖尿病。不同发病年龄层问线粒体DNA3243位点A〉G突变G／A峰值比存在显著性差异[≤25岁（61．6±20．17）％；25～45岁（16．59±8．64）％：〉45岁（6．37±0．59）％，P〈0．01]，且突变G／A峰值比与发病年龄呈显著负相关（r=-0．785，P=0．001）。结论早发糖尿病患者伴耳聋、体重指数正常或较低、有母系遗传倾向可强烈提示线粒体糖尿病的存在。线粒体DNA3243位点A〉G突变G／A峰值比一定程度上可对存在突变者线粒体糖尿病起病年龄及严重程度进行简单预测。

Objective To summarize the clinical phenotype profiles and mitochondrial DNA mutation in maternally inherited diabetes and deafness （ MIDD ） , and to improve the diagnosis and treatment of this disease in clinical practice. Methods Sixteen patients with MIDD in six families from Peking Union Medical College from 2007 to Dec 2014 were confirmed as carrying the mitochondrial （mt ） DNA 3243 A to G mutation. Sanger sequencing was used to detect the mt DNA 3243 A to G mutation. The peak height G/A ratio was used to determine mutation heteroplasmy levels. Results The patients with early onset of diabetes （35.0 ± 14.6 years）, deafness, normal or lower body mass index （ BMI）, and maternal hereditary tendency suggested the diagnosis of MIDD. The peak height G/A ratio was significantly different according to the onset age of MIDD [ ≤25 years （ 61.6± 20.17 ） % ; 25-45 years （ 16.59 ± 8.64） % ; 〉45 years （ 6.37 ±0. 59 ） % ; P〈0. 01 ]. The peak height G/A ratio was negatively correlated with the onset age of MIDD （ r = -0. 785, P = 0. 001 ）. Conclusion Early onset of diabetes with deafness, normal/ lower BMI, and maternal hereditary tendency strongly Suggests the diagnosis of MIDD. The peak height G/A ratio might provide a simple prediction regarding the onset age and severity of MIDD.