Recognition of mitochondrial DNA deletion syndrome with non-neuromuscular multisystemic manifestation

Wong, Lee‐Jun C.

doi:10.1097/00125817-200111000-00004

Cited by 29 publications

(24 citation statements)

References 32 publications

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“…Because of the high-density coverage of the mitochondrial genome, most of the break points of deletions can be determined within 10 to 30 bp precision by the oligonucleotide array (Table 1). Because the location and size of large mtDNA deletion do not correlate with disease clinical phenotype or severity, 27 the break points elucidated by oligonucleotide aCGH are sufficient for diagnosis. Thus, tedious PCR/ sequencing procedures can be eliminated.…”

Section: Discussionmentioning

confidence: 99%

Application of dual-genome oligonucleotidearray-based comparative genomic hybridization to the molecular diagnosis of mitochondrial DNA deletion and depletion syndromes

Chinault

Shaw

Brundage

et al. 2009

Genetics in Medicine

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Purpose: Mitochondrial disorders constitute a group of clinically and genetically heterogeneous diseases for which molecular diagnosis has been a challenge. The current procedures for diagnosis of mitochondrial DNA deletion and depletion syndromes based on Southern analysis and quantitative polymerase chain reaction are particularly inefficient for determining important parameters of deletion endpoints and percent heteroplasmy. We have developed an improved approach for routine analyses of these disorders in a clinical laboratory. Methods: A customdesigned oligonucleotide array-based comparative genomic hybridization platform was developed to provide both tiled coverage of the entire 16.6-kb mitochondrial genome and high-density coverage of nuclear genes involved in mitochondrial biogenesis and function, for quick evaluation of mitochondrial DNA deletion and depletion. Results: For initial validation, the performance of this array was characterized in 20 samples with known mitochondrial DNA deletions and 12 with apparent depletions. All previously known deletions were clearly detected and the break points were correctly identified by the oligonucleotide array-based comparative genomic hybridization, within the limits of resolution of the array. The extent of mitochondrial DNA depletion and the percentage of deletion heteroplasmy were estimated using an automated computational approach that gave results comparable to previous methods. Conclusions from subsequent application of this approach with Ͼ300 new clinical samples have been in 100% concordance with those from standard methods. Finally, for one sample, we were able to identify an intragenic deletion in a nuclear gene that was responsible for the observed mitochondrial DNA depletion. Conclusion: We conclude that this custom array is capable of reliably detecting mitochondrial DNA deletion with elucidation of the deletion break points and the percentage of heteroplasmy. In addition, simultaneous detection of the copy number changes in both nuclear and mitochondrial genomes makes this dual genome array of tremendous value in the diagnoses of mitochondrial DNA depletion syndromes. Genet Med 2009:11(7): 518 -526.

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Section: Discussionmentioning

confidence: 99%

Application of dual-genome oligonucleotidearray-based comparative genomic hybridization to the molecular diagnosis of mitochondrial DNA deletion and depletion syndromes

Chinault

Shaw

Brundage

et al. 2009

Genetics in Medicine

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“…These factors may vary greatly between organs within an affected individual. However, it has been shown that the level of heteroplasmy in patients with younger age at presentation is similar in blood, muscle, and other tissues, while those patients with older age at onset of disease tend to have higher levels of heteroplasmy in muscle [5]. Owing to her young age and the presence of heteroplasmy in blood leukocytes, no further heteroplasmy characterization was undertaken in the patient presented here.…”

Section: Discussionmentioning

confidence: 81%

A mitochondrial DNA deletion presenting with corneal clouding and severe Fanconi syndrome

et al. 2012

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“…Our recent studies of mtDNA deletion syndromes suggest that there might be tissue-specific elimination of mutant mtDNA with the common 5-kb deletion but not the mtDNA with novel deletions. 32 It is conceivable that similar mechanisms of tissue-specific selection of mtDNA point mutations may also take place.…”

Section: Discussionmentioning

confidence: 99%

“…4,[23][24][25] The restriction enzymes used for A3243G, A8344G, G8363A, T8993G, and T8993C were HaeIII, BglI, HphI, AvaI, and MspI, respectively. 4,[23][24][25] Briefly, the PCR products were labeled with [␣- 32 P]dCTP in the last cycle PCR followed by restriction enzyme digestion. 26 The detailed conditions have been described in the literature.…”

Section: Mutation Detection and Quantificationmentioning

confidence: 99%

Intergenerational transmission of pathogenic heteroplasmic mitochondrial DNA

Wong¹,

Wong²,

Liu

2002

Genetics in Medicine

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Purpose: To study the pattern of intergenerational transmission of pathogenic mitochondrial DNA with heteroplasmic A3243G, G8363A, A8344G, T8993G, and T8993C mutations. Methods: The mutant load in the carrier mother and her offspring was measured in a total of 79 transmissions. Statistical analysis was performed to determine whether the intergenerational change in heteroplasmic mutant mtDNA is significant. Results: Our results demonstrate that A3243G and T8993G mutant mtDNAs are significantly increased in blood, hair follicles, and buccal mucosal cells, during intergenerational transmission, whereas the intergenerational increase in T8993C and A8363G mutant mtDNA is not significant. Unlike previous reports, in one large family with A8344G mutation, the mutant load was slightly increased, instead of decreased, during transmission. There is no significant difference in the intergeneration transmission of mutant mtDNA to male or female offspring.

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Recognition of mitochondrial DNA deletion syndrome with non-neuromuscular multisystemic manifestation

Cited by 29 publications

References 32 publications

Application of dual-genome oligonucleotidearray-based comparative genomic hybridization to the molecular diagnosis of mitochondrial DNA deletion and depletion syndromes

Application of dual-genome oligonucleotidearray-based comparative genomic hybridization to the molecular diagnosis of mitochondrial DNA deletion and depletion syndromes

A mitochondrial DNA deletion presenting with corneal clouding and severe Fanconi syndrome

Intergenerational transmission of pathogenic heteroplasmic mitochondrial DNA

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