The two locus control of Leber hereditary optic neurophathy and a high penetrance in Japanese pedigrees

• Published in: Human genetics 1993-05, Vol.91 (4), p.339-341
• Main Authors: NAKAMURA, M, FUJIWARA, Y, YAMAMOTO, M
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; genes; Leber hereditary optic neuropathy; linkage; man; Medical sciences; Ophthalmology; pedigree; Retinopathies; X chromosome
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/BF00217353

The maternal transmission of Leber hereditary optic neuropathy (LHON) can be explained by the mitochondrial DNA mutation. However, the characteristic mode of inheritance, i.e. male predominance and reduced penetrance with late onset in females, suggests the simultaneous involvement of an X-linked gene in development of optic atrophy. We have assessed such a two-locus model of mitochondrial and X-linked genes in Japanese LHON pedigrees. The goodness-of-fit test on individual male sibship data with a presumed heterozygous mother from maternal lines showed an excellent fit for the 1:1 segregation of a putative X-linked gene, thus supporting the two-locus model in Japanese pedigrees tested. A calculated frequency of the X-linked gene was 0.10. We could not determine whether the present value is different from the reported one (= 0.08). On the other hand, the estimated penetrance for a heterozygous female was 0.196 plus or minus 0.039, which was about twice as high as the reported value (= 0.111) with a 5% level of significance. Such a high penetrance may primarily arise from a low threshold of LHON manifestation, suggesting the ethnic difference between the LHON pedigrees in Japan and in other countries.