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

Phasukkijwatana, Nopasak; Chuenkongkaew, Wanicha; Suphavilai, Rungnapa; Luangtrakool, Komon; Kunhapan, Bussaraporn; Lertrit, Patcharee

doi:10.1007/s10038-006-0073-6

Cited by 14 publications

(7 citation statements)

References 19 publications

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“…A lower prevalence of heteroplasmy in [24]. Analyses of four large Thai LHON pedigrees spanning four to six generations strongly suggested that the transmission of the heteroplasmic G11778A mutation is under selective pressure in favor of the mutated allele and that heteroplasmy influences the disease expression [25].…”

Section: Discussionmentioning

confidence: 99%

Late-onset Leber hereditary optic neuropathy mimicking Susac’s syndrome

et al. 2010

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Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder characterized by bilateral painless optic atrophy and blindness. It usually occurs in young men in association with three major mutations in the mitochondrial genome (mtDNA). We report a patient with a history of alcohol abuse who developed at age 63 years visual impairment, sensorineural hearing loss, and memory dysfunction, suggestive of Susac's syndrome. The patient carried the heteroplasmic mt. 11778G>A mutation on the T2e mtDNA haplogroup. It remains unclear if chronic alcohol abuse combined with the mitochondrial genetic background prompted an aged-related neurodegeneration or deferred the onset of the LHON disease.

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Section: Discussionmentioning

confidence: 99%

Late-onset Leber hereditary optic neuropathy mimicking Susac’s syndrome

et al. 2010

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“…31 On the other hand, CIs of other variants were Ͻ70%, indicating that these variants may not be functionally significant. Here, the ND6 I58V variant, which is a haplogroup M10-specific variant, 25,26 was involved in LHON in Chinese families, 32 the CO3 L175F variant was associated with LHON in Thai families, 33 and the CYTB I189V variant was found in hypertensive individuals. 34 Furthermore, the CYTB I189V, L292R, and S297A variants appear to be novel.…”

Section: Mitochondrial Dna Analysismentioning

confidence: 90%

Leber's Hereditary Optic Neuropathy Affects Only Female Matrilineal Relatives in Two Chinese Families

Wang

Tong

et al. 2010

Invest. Ophthalmol. Vis. Sci.

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Only female matrilineal relatives with a wide range of penetrance, severity, and age at onset of optic neuropathy in these two Chinese pedigrees showed the involvement of X-linked or autosomal recessive modifier genes in the phenotypic manifestation of the G11778A mutation. Furthermore, mitochondrial haplogroup-specific variants, together with epigenetic and environmental factors, may contribute to the phenotypic manifestation of the primary LHON-associated G11778A mutation in these pedigrees.

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“…Individuals with 11778/ND4, 3460/ND1, and 14484/ND6 mutations showed levels of heteroplasmy equal to 5.6%, 40% and 36.4%, respectively, [49]. However, a study analysing four large Thai LHON pedigrees showed a prevalence of 37% of heteroplasmic 11778/ND4 mtDNA [50, 51]. In heteroplasmic families, the level of heteroplasmy can vary extensively between generations and also between offspring in the same family due to a genetic bottle neck effect of mitochondrial distribution occurring in the early stages of oocyte formation [48, 52–55].…”

Section: Heteroplasmy and Incomplete Penetrancementioning

confidence: 99%

Leber's Hereditary Optic Neuropathy-Gene Therapy: From Benchtop to Bedside

Koilkonda

Guy

2011

Journal of Ophthalmology

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Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disorder caused by point mutations in mitochondrial DNA (mtDNA). Most cases are due to mutations in genes encoding subunits of the NADH-ubiquinone oxidoreductase that is Complex I of the electron transport chain (ETC). These mutations are located at nucleotide positions 3460, 11778, or 14484 in the mitochondrial genome. The disease is characterized by apoplectic, bilateral, and severe visual loss. While the mutated mtDNA impairs generation of ATP by all mitochondria, there is only a selective loss of retinal ganglion cells and degeneration of optic nerve axons. Thus, blindness is typically permanent. Half of the men and 10% of females who harbor the pathogenic mtDNA mutation actually develop the phenotype. This incomplete penetrance and gender bias is not fully understood. Additional mitochondrial and/or nuclear genetic factors may modulate the phenotypic expression of LHON. In a population-based study, the mtDNA background of haplogroup J was associated with an inverse relationship of low-ATP generation and increased production of reactive oxygen species (ROS). Effective therapy for LHON has been elusive. In this paper, we describe the findings of pertinent published studies and discuss the controversies of potential strategies to ameliorate the disease.

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

Cited by 14 publications

References 19 publications

Late-onset Leber hereditary optic neuropathy mimicking Susac’s syndrome

Late-onset Leber hereditary optic neuropathy mimicking Susac’s syndrome

Leber's Hereditary Optic Neuropathy Affects Only Female Matrilineal Relatives in Two Chinese Families

Leber's Hereditary Optic Neuropathy-Gene Therapy: From Benchtop to Bedside

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