Rapid shift in genotype of human mitochondrial DNA in a family with Leber's hereditary optic neuropathy

Bolhuis, P. A.; Bleeker‐Wagemakers, E. M.; Ponne, Nico J.; Schooneveld, Mary J. van; Westerveld, A.; Bogert, Coby Van den; Tabak, Henk F.

doi:10.1016/0006-291x(90)90490-e

Cited by 72 publications

(22 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The average mutation load in the mothers (n=17) was 44.6±26.1% (median: 44%), while that in the offspring (n = 37) was 64.4±30.1% (median: 70%). These results are in accordance with those of several other studies (Bolhuis et al 1990;Howell et al 1994;Jacobi et al 2001;Savontaus 1995;Smith et al 1993), but not with a recent analysis of data from published pedigrees by Chinnery et al (2001).…”

Section: Heteroplasmic Transmissionsupporting

confidence: 92%

“…Various studies report the rapid segregation of LHON mutations from a low level of heteroplasmy to a practically homoplasmic level in only a few generations (Bolhuis et al 1990;Howell et al 1994;Huoponen 2001;Jacobi et al 2001;Vilkki et al 1990). This was also observed in our pedigrees, the most evident of which was the shift from 18% (F09, II-1) to homoplasmy (F09, III-10 and III-15) over only one generation (Fig.…”

Section: Heteroplasmic Transmissionmentioning

confidence: 99%

“…It is still inconclusive as to whether the transmission of heteroplasmic LHON mutations from one generation to the next is a random or a selective process. While the study of a number of pedigrees has found a trend towards an increasing proportion of the LHON mutation in successive generations (Bolhuis et al 1990;Howell et al 1994;Jacobi et al 2001;Savontaus 1995;Smith et al 1993), suggesting a selection for mutant alleles, other studies have found inconsistent results. Consequently, currently accepted opinion questions the selective process, supporting instead a random process (Chinnery et al 2001;Ghosh et al 1996;Harding et al 1995).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Transmission of heteroplasmic G11778A in extensive pedigrees of Thai Leber hereditary optic neuropathy

et al. 2006

View full text Add to dashboard Cite

Section: Heteroplasmic Transmissionsupporting

confidence: 92%

Section: Heteroplasmic Transmissionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Transmission of heteroplasmic G11778A in extensive pedigrees of Thai Leber hereditary optic neuropathy

et al. 2006

View full text Add to dashboard Cite

“…mtDNA heteroplasmy was also found in some other LHON patients (25). Of interest, a rapid meiotic segregation rate ofthe heteroplasmic family members with LHON was reported (26,27). This observation-i.e., a shift from heteroplasmy to homoplasmy in one or two generations-suggests that heteroplasmy may not be maintained for many generations.…”

Section: Resultsmentioning

confidence: 74%

X chromosome-linked and mitochondrial gene control of Leber hereditary optic neuropathy: evidence from segregation analysis for dependence on X chromosome inactivation.

Rotter

1991

Proc. Natl. Acad. Sci. U.S.A.

151

View full text Add to dashboard Cite

Leber hereditary optic neuropathy (LHON) has been shown to involve mutation(s) of mitochondrial DNA, yet there remain several confusing aspects of Its inheritance not explained by mitochondrial inheritance alone, including male predominance, reduced penetrance, and a later age of onset in females. By extending segregation analysis methods to disorders that involve both a mitochondrial and a nuclear gene locus, we show that the available pedigree data for LHON are most consistent with a two-locus disorder, with one responsible gene being mitochondrial and the other nuclear and X chromosome-linked. Furthermore, we have been able to extend the two-locus analytic method and demonstrate that a proportion of affected females are likely heterozygous at the X chromosome-linked locus and are affected due to unfortunate X chromosome inactivation, thus providing an explanation for the later age of onset in females. The estimated penetrance for a heterozygous female is 0.11 ± 0.02. The calculated frequency of the X chromosome-linked gene for LHON is 0.08. Among affected females, 60% are expected to be heterozygous, and the remainder are expected to be homozygous at the responsible X chromosome-linked locus.

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

Rapid shift in genotype of human mitochondrial DNA in a family with Leber's hereditary optic neuropathy

Cited by 72 publications

References 7 publications

Transmission of heteroplasmic G11778A in extensive pedigrees of Thai Leber hereditary optic neuropathy

Transmission of heteroplasmic G11778A in extensive pedigrees of Thai Leber hereditary optic neuropathy

X chromosome-linked and mitochondrial gene control of Leber hereditary optic neuropathy: evidence from segregation analysis for dependence on X chromosome inactivation.

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

Contact Info

Product

Resources

About