Variable Genotype of Leber's Hereditary Optic Neuropathy Patients

Lott, Marie T.; Voljavec, Alexander S.; Wallace, Douglas C.

doi:10.1016/s0002-9394(14)72429-8

Cited by 97 publications

(20 citation statements)

References 17 publications

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“…Studies addressing tissue distribution of the heteroplasmic LHON mutations are still few in number and have mainly relied on comparisons between blood and hair follicle analyses (Lott et al, 1990;Yen et al, 1992). Furthermore, in these studies, the quantification of the amount of mutated mtDNA between the tissues was not performed.…”

Section: Resultsmentioning

confidence: 99%

Tissue distribution of the ND4/11778 mutation in heteroplasmic lineages with Leber hereditary optic neuropathy

et al. 1997

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Section: Resultsmentioning

confidence: 99%

Tissue distribution of the ND4/11778 mutation in heteroplasmic lineages with Leber hereditary optic neuropathy

et al. 1997

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“…A lower percentage of mutant mtDNA was found in the hair than in the blood (Lott et al 1990;Yen et al 1992); the same percentage of heteroplasmy was found in the hair and urinary tract epitheliums (Barbiroli et al 1995); homoplasmic patterns were found in the optochiasmal arachnoidea, hair, skeletal muscle, etc. (Shimo-oku et al 1996).…”

Section: Discussionmentioning

confidence: 99%

“…However, as only one stained histopathological preparation per tissue was used, and as her blood could not be analysed, there are limitations as to the interpretation of tissue distribution of mutant mtDNA. However, the fact that her descendants showed homoplasmy of mutant mtDNA in the blood might suggest a rapid accumulation of mutant mtDNA over generations (Bolhuis et al 1990;Lott et al 1990;Vilkki et al 1990;Smith et al 1993).…”

Section: Discussionmentioning

confidence: 99%

Detection of mitochondrial DNA nucleotide 11778 point mutation of Leber hereditary optic neuropathy from archival stained histopathological preparations

Mitani

Miyazaki

Hayashi

et al. 1998

Acta Ophthalmologica Scandinavica

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ABSTRACT. Purpose: We evaluated the availability of archival histopathological preparations for genetic diagnosis of Leber hereditary optic neuropathy (LHON).Methods: Preparations of various tissues of an autopsied case of LHON, and of the optochiasmal arachnoidea of nine cases of bilateral optic neuropathy (BON) were studied to determine the presence of a point mutation of the mitochondrial DNA nucleotide (nt) 11778 using PCR method. Results: An nt11778 point mutation was detected in all preparations of the autopsied case. Five preparations out of six BON cases who were diagnosed as LHON based on positive family history, revealed this point mutation. This mutation was also detected in two of three BON patients with no family history of the disease. Conclusion:The archival preparations were found to be available as materials of genetic diagnosis for LHON, which indicated that it would be capable to reevaluate retrospectively the pedigree of LHON and BON cases.Key words: Leber hereditary optic neuropathy -bilateral optic neuropathy -genetic diagnosismtDNA nt11778 point mutation -stained histopathological preparations.

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“…This makes the heteroplasmy hypothesis even more unlikely. Besides many observations in humans which suggest that homoplasmy is more frequent [Giles et al, 1980;Vilkki et at., 19891, rapid cellular segregation (in a stochastic fashion) from a heteroplasmic state to a homoplasmic state in various organisms has been reported [Hauswirth and Laipis, 1985;Attardi, 1988, 1989;de Stordeur et al, 1989;Niki et al, 1989;Bolhuis et a]., 1990;Lott et al, 1990;Koehler et al, 19911. Several theoretical analyses, which utilized the infinite alleles model in population genetics, have shown that mtDNA heteroplasmy is a transitory state, while the homoplasmic state is more stable [Birky, 1983;Birky et al, 1983, 19891. In the present study, a relatively high frequency of the autosomal gene was obtained.…”

Section: Discussionmentioning

confidence: 99%

A form of sensorineural deafness is determined by a mitochondrial and an autosomal locus: Evidence from pedigree segregation analysis

Shohat

Jaber

et al. 1993

Genetic Epidemiology

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We have previously reported a large Israeli-Arab pedigree with sensorineural deafness possibly determined simultaneously by two loci--one mitochondrial, and one autosomal recessive. This was analyzed by extending classic segregation analysis methods to the many nuclear families derived from the maternal line pedigree. Here we expand this pedigree and extend our analysis by using the regressive models for segregation analysis on the entire pedigree. The corresponding REGD computer program was utilized and the marrying-in males' and paternal line members' affection statuses were assigned as unknown to accommodate the exclusive maternal transmission pattern. For the autosomal locus, a simple autosomal recessive (q = 0.52) model with a nearly complete penetrance (0.93) was found to be the best-fitting model. Equally importantly, we were also able to use the power of the regressive models to test the hypothesis of mitochondrial heteroplasmy as an alternative for the proposed autosomal locus. We found no evidence for the heteroplasmy hypothesis as an explanation for the incomplete maternal transmission of deafness in this pedigree. Thus, even if the mitochondrial mutation occurred in a heteroplasmic distribution in the family members, this could not explain the familial aggregation in this pedigree, and an autosomal recessive locus is still required. These results provide further support for the concept that the sensorineural deafness occurring in this large Israeli-Arab pedigree results from simultaneous involvement of two genes at two different loci, one mitochondrial and likely homoplasmic, and the other autosomal and recessive.

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Variable Genotype of Leber's Hereditary Optic Neuropathy Patients

Cited by 97 publications

References 17 publications

Tissue distribution of the ND4/11778 mutation in heteroplasmic lineages with Leber hereditary optic neuropathy

Tissue distribution of the ND4/11778 mutation in heteroplasmic lineages with Leber hereditary optic neuropathy

Detection of mitochondrial DNA nucleotide 11778 point mutation of Leber hereditary optic neuropathy from archival stained histopathological preparations

A form of sensorineural deafness is determined by a mitochondrial and an autosomal locus: Evidence from pedigree segregation analysis

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