Influence of mutation type on clinical expression of Leber hereditary optic neuropathy.
OBJECTIVE
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.


METHODS
Observational, retrospective population cohort study.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Genetics and Cell Biology, Maastricht University, Maastricht, The Netherlands. liesbeth.spruijt@gen.unimaas.nl
Liesbeth
L
Spruijt
Dinanda N
DN
Kolbach
Rene F
RF
de Coo
Astrid S
AS
Plomp
Noel J
NJ
Bauer
Hubertus J
HJ
Smeets
Christine E M
CE
de Die-Smulders
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D009154:Mutation; D009426:Netherlands / Q000453:epidemiology; D029242:Optic Atrophy, Hereditary, Leber / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D019683:Penetrance; D015995:Prevalence; D012189:Retrospective Studies; D017678:Sex Distribution; D014786:Vision Disorders / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology
D004272:DNA, Mitochondrial