Spruijt Liesbeth, Kolbach Dinanda N, de Coo Rene F, Plomp Astrid S, Bauer Noel J, Smeets Hubertus J, de Die-Smulders Christine E M
Department of Genetics and Cell Biology, Maastricht University, Maastricht, The Netherlands.
Am J Ophthalmol. 2006 Apr;141(4):676-82. doi: 10.1016/j.ajo.2005.11.007.
The aim of this research was to determine the molecular factors of influence on the clinical expression of Leber hereditary optic neuropathy (LHON), which might aid in counseling LHON patients and families. The prevalence of LHON in the Dutch population was determined.
Observational, retrospective population cohort study.
The clinical characteristics of LHON patients of 25 families, previously described in 1963, were reevaluated. The mutation and haplotype were determined in the DNA of one affected LHON patient per family. The genotype of their relatives could be deducted, enabling us to evaluate retrospectively the genotype-phenotype correlation. The prevalence of LHON was determined on the basis of anamnestic evaluation of patients in 1963 and by using population registers of that period.
The LHON mutation does not influence disease penetrance (50% in male subjects; 10% to 20% in female subjects). More than half of the patients with the 14484 mutation exhibit a partial recovery of vision, regardless of the acuteness of disease onset (P = .001), whereas only 22% of the 11778 carriers and 15.4% of the 3460 carriers recovered. The recovery did not take place within the first year after onset and was uncommon after four years. The onset of LHON is in general very acute but might be more gradual in 11778 carriers and in children. The calculated prevalence of LHON in the Dutch population (1/39,000) is very likely an underestimation caused by a selection bias of familial cases in the original study.
The LHON genotype influences the recovery of vision and disease onset but is unrelated to age, acuteness of onset, or gender. The genotype does not influence disease penetrance. Children might exhibit a slower onset of disease.
本研究旨在确定影响Leber遗传性视神经病变（LHON）临床表型的分子因素，这可能有助于为LHON患者及其家属提供咨询。同时确定了荷兰人群中LHON的患病率。
观察性、回顾性人群队列研究。
对1963年之前描述的25个家庭的LHON患者的临床特征进行重新评估。确定每个家庭中一名受影响的LHON患者DNA中的突变和单倍型。可以推断出其亲属的基因型，从而使我们能够回顾性评估基因型与表型的相关性。根据1963年患者的回忆性评估以及该时期的人口登记册确定LHON的患病率。
LHON突变不影响疾病的外显率（男性为50%；女性为10%至20%）。超过一半携带14484突变的患者视力有部分恢复，无论疾病发作的急性程度如何（P = 0.001），而携带11778突变的患者中只有22%恢复，携带3460突变的患者中只有15.4%恢复。恢复并非发生在发病后的第一年内，四年后也不常见。LHON的发作通常非常急性，但在携带11778突变的患者和儿童中可能更为渐进。计算得出的荷兰人群中LHON的患病率（1/39,000）很可能因原始研究中家族性病例的选择偏倚而被低估。
LHON基因型影响视力恢复和疾病发作，但与年龄、发作急性程度或性别无关。该基因型不影响疾病外显率。儿童可能表现出较慢的疾病发作。
