PT  - JOURNAL ARTICLE
AU  - P Y W Man
AU  - D M Turnbull
AU  - P F Chinnery
TI  - Leber hereditary optic neuropathy
AID  - 10.1136/jmg.39.3.162
DP  - 2002 Mar 01
TA  - Journal of Medical Genetics
PG  - 162--169
VI  - 39
IP  - 3
4099  - http://jmg.bmj.com/content/39/3/162.short
4100  - http://jmg.bmj.com/content/39/3/162.full
SO  - J Med Genet2002 Mar 01; 39
AB  - Leber hereditary optic neuropathy (LHON) is a mitochondrial genetic disease that preferentially causes blindness in young adult males, affecting about 1 in 25 000 of the British population. It is characterised by bilateral subacute loss of central vision owing to focal degeneration of the retinal ganglion cell layer and optic nerve. Over 95% of LHON cases are primarily the result of one of three mitochondrial DNA (mtDNA) point mutations, G3460A, G11778A, and T14484C, which all involve genes encoding complex I subunits of the respiratory chain. An intriguing feature of LHON is that only ∼50% of males and ∼10% of females who harbour a pathogenic mtDNA mutation actually develop the optic neuropathy. This marked incomplete penetrance and gender bias imply that additional mitochondrial and/or nuclear genetic factors must be modulating the phenotypic expression of LHON. It is also likely that environmental factors contribute to the onset of visual failure. However, these secondary precipitating factors remain poorly defined at present. In this review, we describe the natural history of this optic nerve disorder and highlight issues relating to clinical diagnosis, management, and genetic counselling. We also discuss the findings of recently published studies and the light they shed on the complex aetiology and pathophysiology of LHON.