mtDNA Haplotype Analysis in Finnish Families with Leber Hereditary Optic Neuroretinopathy

Lamminen, Tarja; Huoponen, Kirsi; Sistonen, Pertti; Juvonen, Vesa; Aula, Pertti; Nikoskelainen, Eeva; Savontaus, Marja‐Liisa

doi:10.1159/000484777

Cited by 38 publications

(29 citation statements)

References 15 publications

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“…Haplogroup and phylogenetic analysis of LHON patients have, however, shown that two of the three primary LHON mutations, at np 11778 and 14484, tend to be associated with European mtDNA haplogroup J. 11 23 24 Additional evidence supporting a role for mtDNA haplogroups as a risk factor in disease expression has also recently been reported with the observation that migraine associated stroke is more common in individuals belonging to haplogroup U than would be expected on a random basis. 25 The site, or sites, within these haplogroups that influence penetrance or expression have not been identified.…”

Section: Discussionmentioning

confidence: 98%

The role of mitochondrial haplogroups in primary open angle glaucoma

Andrews

Ressiniotis²,

Turnbull³

et al. 2006

British Journal of Ophthalmology

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Aim:To investigate a possible association between mitochondrial haplogroups and primary open angle glaucoma (POAG). Methods: Genomic DNA was extracted from 140 POAG patients and 75 healthy individuals. Restriction enzyme digest analysis of polymerase chain reaction (PCR) amplified fragments was used to determine the mitochondrial haplogroup of each patient and control. Results: The median age was 73 years for the POAG patients (range 51-87, SD 8.01) and 78 years for the controls (range 68-90, SD 4.4). Mean IOP was 20.8 mm Hg for the patients (SD 2.6) and 16.2 mm Hg for the controls (SD 3.4). Median cup/disc ratio was 0.8 and 0

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Section: Discussionmentioning

confidence: 98%

The role of mitochondrial haplogroups in primary open angle glaucoma

Andrews

Ressiniotis²,

Turnbull³

et al. 2006

British Journal of Ophthalmology

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“…Haplogroup J, one of several mitochondrial haplogroups found in central Europeans, has been associated with the 11778 and 14484 mutations in LHON,86,123 and a meta-analysis of 159 European pedigrees has suggested the penetrance of these two primary mutations is increased on a haplogroup J background 91. The 3460 mutation, on the other hand, although distributed equally among haplogroups, was more often expressed phenotypically on a haplogroup K background.…”

Section: Optic Neuropathymentioning

confidence: 99%

The Neuro-ophthalmology of Mitochondrial Disease

Fraser

Biousse

Newman

2010

Survey of Ophthalmology

223

250

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Mitochondrial diseases frequently manifest neuro-ophthalmologic symptoms and signs. Because of the predilection of mitochondrial disorders to involve the optic nerves, extraocular muscles, retina, and even the retrochiasmal visual pathways, the ophthalmologist is often the first physician to be consulted. Disorders caused by mitochondrial dysfunction can result from abnormalities in either the mitochondrial DNA or in nuclear genes which encode mitochondrial proteins. Inheritance of these mutations will follow patterns specific to their somatic or mitochondrial genetics. Genotype-phenotype correlations are inconstant, and considerable overlap may occur among these syndromes. The diagnostic approach to the patient with suspected mitochondrial disease entails a detailed personal and family history, careful ophthalmic, neurologic, and systemic examination, directed investigations, and attention to potentially life-threatening sequelae. Although curative treatments for mitochondrial disorders are currently lacking, exciting research advances are being made, particularly in the area of gene therapy. Leber hereditary optic neuropathy, with its window of opportunity for timely intervention and its accessibility to directed therapy, offers a unique model to study future therapeutic interventions. Most patients and their relatives benefit from informed genetic counseling.

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“…The first strong evidence of such a haplogroup effect was reported in 1997, again the result of studying LHON. Four concomitant investigations performed on patients of diverse European origins revealed that the LHON mutations 11778/ND4 and 14484/ND6 were preferentially associated with the western Eurasian haplogroup J (Brown et al 1997;Hofmann et al 1997;Lamminen et al 1997;Torroni et al 1997). This observation led to the idea that the mutational motif in ND subunits that defines haplogroup J-4216C/ND1-10398G/ND3-13708A/ND5-might increase the penetrance of the 11778/ND4 and 14484/ND6 mutations and the risk of disease expression (Torroni et al 1997).…”

mentioning

confidence: 99%

Haplogroup Effects and Recombination of Mitochondrial DNA: Novel Clues from the Analysis of Leber Hereditary Optic Neuropathy Pedigrees

Carelli

Achilli

Valentino

et al. 2006

The American Journal of Human Genetics

168

151

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The mitochondrial DNA (mtDNA) of 87 index cases with Leber hereditary optic neuropathy (LHON) sequentially diagnosed in Italy, including an extremely large Brazilian family of Italian maternal ancestry, was evaluated in detail. Only seven pairs and three triplets of identical haplotypes were observed, attesting that the large majority of the LHON mutations were due to independent mutational events. Assignment of the mutational events into haplogroups confirmed that J1 and J2 play a role in LHON expression but narrowed the association to the subclades J1c and J2b, thus suggesting that two specific combinations of amino acid changes in the cytochrome b are the cause of the mtDNA background effect and that this may occur at the level of the supercomplex formed by respiratory-chain complexes I and III. The families with identical haplotypes were genealogically reinvestigated, which led to the reconnection into extended pedigrees of three pairs of families, including the Brazilian family with its Italian counterpart. The sequencing of entire mtDNA samples from the reconnected families confirmed the genealogical reconstruction but showed that the Brazilian family was heteroplasmic at two control-region positions. The survey of the two sites in 12 of the Brazilian subjects revealed triplasmy in most cases, but there was no evidence of the tetraplasmy that would be expected in the case of mtDNA recombination.

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mtDNA Haplotype Analysis in Finnish Families with Leber Hereditary Optic Neuroretinopathy

Cited by 38 publications

References 15 publications

The role of mitochondrial haplogroups in primary open angle glaucoma

The role of mitochondrial haplogroups in primary open angle glaucoma

The Neuro-ophthalmology of Mitochondrial Disease

Haplogroup Effects and Recombination of Mitochondrial DNA: Novel Clues from the Analysis of Leber Hereditary Optic Neuropathy Pedigrees

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