Reevaluation of the linkage of an optic atrophy susceptibility gene to X-chromosomal markers in Finnish families with Leber hereditary optic neuroretinopathy (LHON)
One of the commonest reasons for sudden-onset optic nerve degeneration in young men can be attributed to maternally inherited Leber hereditary optic neuroretinopathy (LHON) (Nikoskelainen et al. 1987). Specific point mutations at either np 11778 (Wallace et al. 1988) or np 3460 (Howell et al. 1991; Huoponen et al. 1991) in mitochondrial DNA (mtDNA) encoding for respiratory enzyme complex I subunits (i.e., ND4 or ND1) can be found in 70% of families. These mutations exist as being either homoplasmic or heteroplasmic, but the correlation between the degree of heteroplasmy and the risk of developing optic atrophy is far from clear (Holt et al. 1989; Vilkki et al. 1990). Neither does heteroplasmy explain the strong male bias seen in LHON families, when the sex ratio of patients with visual impairment is observed. Earlier results indicated that susceptibility to optic atrophy in Finnish families with LHON was probably determined by an X-chromosomal gene closely linked to DXS7. Contradictory results prompted reevaluation of the existence of an X-chromosomal visual loss susceptibility gene in Finnish LHON families. The results of this present study clearly demonstrate that the earlier close linkage to DXS7 is implausible. The altered Z is due to revised pedigrees, the use of liability classes, and separation of the families according to the associated mtDNA mutation. 16 refs., 1 fig., 1 tab.
- OSTI ID:
- 5914230
- Journal Information:
- American Journal of Human Genetics; (United States), Vol. 53:1; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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EYES
HEREDITARY DISEASES
HUMAN X CHROMOSOME
GENETIC MAPPING
RETINA
ATROPHY
FINLAND
GENE MUTATIONS
MITOCHONDRIA
BODY
BODY AREAS
CELL CONSTITUENTS
CHROMOSOMES
DEVELOPED COUNTRIES
DISEASES
EUROPE
FACE
HEAD
HETEROCHROMOSOMES
HUMAN CHROMOSOMES
MAPPING
MUTATIONS
ORGANS
PATHOLOGICAL CHANGES
SCANDINAVIA
SENSE ORGANS
WESTERN EUROPE
X CHROMOSOME
550400* - Genetics
550900 - Pathology