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目的对两个疑似线粒体糖尿病(MDM)的家系行线粒体基因组扫描,以期发现与MDM发病有关的新致病位点。方法对疑似MDM家系所有成员行除D-环区外线粒体基因组测序,并对发现的新突变位点在200例正常对照及100例早发糖尿病患者中的突变频率进行筛查。结果家系1未发现有意义突变,家系2先证者及其母亲和兄弟发现14319T→C突变。该突变位于ND6区,编码氨基酸由天冬酰胺(N)变为天冬氨酸(D),目前尚未见报道。该位点突变在100例早发糖尿病患者及200例正常对照中突变频率分别为6%和5%,差异无统计学意义(P>0.05)。结论家系1未发现致病性突变,可能与线粒体基因的异质性有关。家系2中3例糖尿病患者均发现14319T→C突变,推测该突变可能是该糖尿病家系的主要致病因素。
Objective To investigate the mitochondrial genome of two families with suspected mitochondrial diabetes (MDM) in order to find new pathogenic sites related to the pathogenesis of MDM. Methods All the members of the suspected MDM family were sequenced except mitochondrial genome outside the D-loop region, and the mutation frequencies of the newly discovered mutation sites in 200 normal controls and 100 patients with early-onset diabetes were screened. Results No significant mutations were found in pedigree 1, and 14319T → C mutations were found in pedigree 2 probands, their mothers and their brothers. The mutation is located in the ND6 region, encoding amino acids from asparagine (N) to aspartic acid (D), has not been reported. The frequency of mutation was 6% and 5% respectively in 100 patients with early-onset diabetes and 200 normal controls. There was no significant difference (P> 0.05). Conclusion There was no pathogenic mutation in pedigree 1, which may be related to the heterogeneity of mitochondrial genes. A total of 14319T → C mutations were found in 3 cases of diabetes in family 2, suggesting that this mutation may be the major causative factor in this pedigree.