Oostra R J, Bolhuis P A, Wijburg F A, Zorn-Ende G, Bleeker-Wagemakers E M
The Netherlands Ophthalmic Research Institute, Amsterdam.
J Med Genet. 1994 Apr;31(4):280-6. doi: 10.1136/jmg.31.4.280.
Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease associated with mitochondrial DNA (mtDNA) mutations. We describe the distribution of seven different mtDNA mutations and the clinical findings in 334 LHON patients belonging to 29 families. Mutations described only in LHON at nucleotide positions 11778, 3460, and 14484 were found in 15, two, and nine families respectively. In three families none of these mutations was found. Mutations described in LHON but also in controls at nucleotide positions 15257, 13708, 4917, and 4216 were found in one, 10, three and 12 families respectively. Combinations of mtDNA mutations were found in most families. The patient population mainly consisted of 79.2% to 89.5% males except for one family with only 10 of 17 patients being males (58.9%, p approximately 0.036). In 11 families only the 11778 mutation was found; in this group (WX) the affected males had a mean age of onset of 29.2 years and a mean visual outcome of 0.113. In seven families the 14484, 13708, and 4216 mutations were found; in this group (MA) the affected males had a mean age of onset of 22.0 years and a mean visual outcome of 0.442. In two families no mutation was found at all; in this group (YX) the affected males had a mean age of onset of 18.9 years and a mean visual outcome of 0.167. The mean age of onset in the WX group is significantly higher than in the MA group (p < or = 0.001) and in the YX group (p approximately 0.01). The mean visual outcome in the MA group is significantly better than in the WX group (p </= 0.001) and the YX group (p = 0.05). No significant clinical differences were found between families exhibiting only the 11778 mutation and those with additional mutations at np 13708, 4917, or 4216, suggesting that these mutations are of little phenotypic importance. Other mutations were present in relatively small numbers of patients. These results show that the clinical severity is dependent on the mitochondrial genotype.
Leber遗传性视神经病变（LHON）是一种与线粒体DNA（mtDNA）突变相关的母系遗传性疾病。我们描述了29个家族中334例LHON患者的7种不同mtDNA突变分布及临床发现。仅在LHON中描述的位于核苷酸位置11778、3460和14484的突变分别在15个、2个和9个家族中被发现。在3个家族中未发现这些突变中的任何一种。在LHON中描述但在对照中也存在的位于核苷酸位置15257、13708、4917和4216的突变分别在1个、10个、3个和12个家族中被发现。大多数家族中发现了mtDNA突变的组合。除了一个家族中17例患者仅有10例为男性（58.9%，p约为0.036）外，患者群体主要由79.2%至89.5%的男性组成。在11个家族中仅发现了11778突变；在这个组（WX）中，受影响男性的平均发病年龄为29.2岁，平均视力结果为0.113。在7个家族中发现了14484、13708和4216突变；在这个组（MA）中，受影响男性的平均发病年龄为22.0岁，平均视力结果为0.442。在2个家族中根本未发现突变；在这个组（YX）中，受影响男性的平均发病年龄为18.9岁，平均视力结果为0.167。WX组的平均发病年龄显著高于MA组（p≤0.001）和YX组（p约为0.01）。MA组的平均视力结果显著优于WX组（p≤0.001）和YX组（p = 0.05）。在仅表现出11778突变的家族与在np 13708、4917或4216处有额外突变的家族之间未发现显著的临床差异，这表明这些突变在表型上不太重要。其他突变存在于相对较少数量的患者中。这些结果表明临床严重程度取决于线粒体基因型。
