Optic Atrophy in Leber Hereditary Optic Neuroretinopathy is Probably
Determined by an X-chromosomal Gene Closely Linked to DXS7
J. Vilkki, J. Ott, M.L. Savontaus, P. Aula, E.K. Nikoskelainen
American Journal of Human Genetics , 48(3), 486--491, (1991 Mar)
Abstract
Leber hereditary optic neuroretinopathy (LHON) is a maternally
inherited disease, probably transmitted by mutations in mtDNA. The
variation in the clinical expression of the disease among family
members has remained unexplained, but pedigree data suggest an
involvement of an X-chromosomal factor. We have studied genetic
linkage of the liability to develop optic atrophy to 15 polymorphic
markers on the X chromosome in six pedigrees with LHON. The results
show evidence of linkage to the locus DXS7 on the proximal Xp. Tight
linkage to the other marker loci was excluded. Multipoint linkage
analysis placed the liability locus at DXS7 with a maximum lod score
(Zmax) of 2.48 at a recombination fraction (theta) of .0 and with a
Zmax - 1 support interval theta = .09 distal to theta = .07 proximal
of DXS7. No evidence of heterogeneity was found among different
types of families, with or without a known mtDNA mutation associated
with LHON.
