Influence of Mutation Type on Clinical Expreion of Leber Hereditary Optic Neuropathy Original Reearch Article

Purpoe The aim of thi reearch wa to determine the molecular factor of influence on the clinical expreion of Leber hereditary optic neuropathy (LHON), which might aid in couneling LHON patient and familie. The prevalence of LHON in the Dutch population wa determined. Deign Obervational, retropective population cohort tudy. Method The clinical characteritic of LHON patient of 25 familie, previouly decribed in 1963, were reevaluated. The mutation and haplotype were determined in the DNA of one affected LHON patient per family. The genotype of their relative could be deducted, enabling u to evaluate retropectively the genotype-phenotype correlation. The prevalence of LHON wa determined on the bai of anamnetic evaluation of patient in 1963 and by uing population regiter of that period. Reult The LHON mutation doe not influence dieae penetrance (50% in male ubject; 10% to 20% in female ubject). More than half of the patient with the 14484 mutation exhibit a partial recovery of viion, regardle of the acutene of dieae onet (P = .001), wherea only 22% of the 11778 carrier and 15.4% of the 3460 carrier recovered. The recovery did not take place within the firt year after onet and wa uncommon after four year. The onet of LHON i in general very acute but might be more gradual in 11778 carrier and in children. The calculated prevalence of LHON in the Dutch population (1/39,000) i very likely an underetimation caued by a election bia of familial cae in the original tudy. Concluion The LHON genotype influence the recovery of viion and dieae onet but i unrelated to age, acutene of onet, or gender. The genotype doe not influence dieae penetrance. Children might exhibit a lower onet of dieae.