scholarly journals A Simple Oligonucleotide Biochip Capable of Rapidly Detecting Known Mitochondrial DNA Mutations in Chinese Patients with Leber’S Hereditary Optic Neuropathy (LHON)

2011 ◽  
Vol 30 (4) ◽  
pp. 181-190 ◽  
Author(s):  
Wei-Dong Du ◽  
Gang Chen ◽  
Hui-Min Cao ◽  
Qing-Hui Jin ◽  
Rong-Feng Liao ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Optic Neuropathy ◽  
Transmitted Disease ◽  
Chinese Patients ◽  
Base Substitution ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Leber's Hereditary Optic Neuropathy ◽  
Mtdna Mutations ◽  
Hereditary Optic Neuropathy ◽  
Oligonucleotide Biochip

Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease. Clinically, no efficient assay protocols have been available. In this study, we aimed to develop an oligonucleotide biochip specialized for detection of known base substitution mutations in mitochondrial DNA causing LHON and to investigate frequencies of LHON relevant variants in Anhui region of China. Thirty-two pairs of oligonucleotide probes matched with the mutations potentially linked to LHON were covalently immobilized. Cy5-lablled targets were amplified from blood DNA samples by a multiplex PCR method. Two kinds of primary mutations 11778 G > A and 14484 T > C from six confirmed LHON patients were interrogated to validate this biochip format. Further, fourteen Chinese LHON pedigrees and twenty-five unrelated healthy individuals were investigated by the LHON biochip, direct sequencing and pyrosequencing, respectively. The biochip was found to be able efficiently to discriminate homoplasmic and heteroplasmic mtDNA mutations in LHON. Biochip analysis revealed that twelve of eighteen LHON symptomatic cases from the 14 Chinese pedigree harbored the mutations either 11778G > A, 14484T > C or 3460G > A, respectively, accounting for 66.7%. The mutation 11778G > A in these patients was homoplasmic and prevalent (55.5%, 10 of 18 cases). The mutations 3460G > A and 3394T > C were found to co-exist in one LHON case. The mutation 13708G > A appeared in one LHON pedigree. Smaller amount of sampling and reaction volume, easier target preparation, fast and high-throughput were the main advantages of the biochip over direct DNA sequencing and pyrosequencing. Our findings suggested that primary mutations of 11778G > A, 14484T > C or 3460G > A are main variants of mtDNA gene leading to LHON in China. The biochip would easily be implemented in clinical diagnosis.

scholarly journals Mitochondrial DNA variation of Leber’s Hereditary Optic Neuropathy (LHON) in Western Siberia

2019 ◽  
Author(s):  
E.B. Starikovskaya ◽  
S.A. Shalaurova ◽  
S.V. Dryomov ◽  
A.M. Nazhmidenova ◽  
N.V. Volodko ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Optic Neuropathy ◽  
Western Siberia ◽  
Vision Loss ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Inherited Disease ◽  
Leber's Hereditary Optic Neuropathy ◽  
Mtdna Mutations ◽  
Pathogenic Mutations ◽  
Hereditary Optic Neuropathy

AbstractLeber’s hereditary optic neuropathy (LHON) is a form of disorder caused by pathogenic mutations in a mitochondrial DNA. LHON is maternally inherited disease, which manifests mainly in young adults, affecting predominantly males. Clinically LHON has a manifestation as painless central vision loss, resulting in early onset of disability. Epidemiology of LHON has not been fully investigated yet. In this study, we report 44 genetically unrelated families with LHON manifestation. We performed whole mtDNA genome sequencing and provided genealogical and molecular genetic data on mutations and haplogroup background of LHON patients in the Western Siberia population. Known “primary” pathogenic mtDNA mutations (MITOMAP) were found in 32 families: m.11778G>A represents 53,10% (17/32), m.3460G>A – 21,90% (7/32), m.14484T>C – 18,75% (6/32), and rare m.10663T>C and m.3635G>A represent 6,25% (2/32). We describe potentially pathogenic m.4659G>A in one subject without known pathogenic mutations, and potentially pathogenic m.9444C>T, m.6261G>A, m.9921G>A, m.8551T>C, m.8412T>C, m.15077G>A in families with known pathogenic mutations confirmed. We suppose these mutations could contribute to the pathogenesis of optic neuropathy development. Our results indicate that haplogroup affiliation and mutational spectrum of the Western Siberian LHON cohort substantially deviate from those of European populations.

scholarly journals Can the effects of the mitochondrial DNA mutations found in Leber’s hereditary optic neuropathy be protective against the development of cluster headache in smokers?

2020 ◽  
Vol 3 ◽  
pp. 251581632093957 ◽  
Author(s):  
Todd D Rozen
Keyword(s):  
Mitochondrial Dna ◽  
Cluster Headache ◽  
Protective Effect ◽  
Optic Neuropathy ◽  
Vision Loss ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Leber's Hereditary Optic Neuropathy ◽  
Tobacco Exposure ◽  
Mtdna Mutations ◽  
Hereditary Optic Neuropathy

Is it possible that some mitochondrial DNA (mtDNA) mutations enhance the risk of developing a headache disorder while other mutations actually confer a protective effect? Mitochondrial disorders have been linked to migraine but very rarely to cluster headache (CH). The true pathogenesis of CH is unknown but a linkage to cigarette smoking is irrefutable. Leber’s hereditary optic neuropathy is a syndrome of bilateral vision loss that typically manifests in a patient’s 20s and 30s, is male predominant, and its sufferers are heavy smokers and heavy drinkers. Tobacco exposure is so linked to the condition that only smokers appear to develop vision loss while nonsmokers remain unaffected carriers of their mutations. In essence, the Leber’s hereditary optic neuropathy population is the CH population but at present there have been no reported cases of CH in this mitochondrial subgroup. Thus, could the effects of the mtDNA mutations found in Leber’s hereditary optic neuropathy, which involve complex I of the electron transport chain, actually confer a protective effect against the development of CH? This article will delve into this theory.

scholarly journals Mitochondrial DNA Variation of Leber’s Hereditary Optic Neuropathy in Western Siberia

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1574 ◽  
Author(s):  
Elena Starikovskaya ◽  
Sofia Shalaurova ◽  
Stanislav Dryomov ◽  
Azhar Nazhmidenova ◽  
Natalia Volodko ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Optic Neuropathy ◽  
Western Siberia ◽  
Vision Loss ◽  
Molecular Genetic ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Leber's Hereditary Optic Neuropathy ◽  
Mtdna Mutations ◽  
Pathogenic Mutations ◽  
Hereditary Optic Neuropathy

Our data first represent the variety of Leber’s hereditary optic neuropathy (LHON) mutations in Western Siberia. LHON is a disorder caused by pathogenic mutations in the mitochondrial DNA (mtDNA), inherited maternally and presents mainly in young adults, predominantly males. Clinically, LHON manifests itself as painless central vision loss, resulting in early onset of disability. The epidemiology of LHON has not been fully investigated yet. In this study, we report 44 genetically unrelated families with LHON manifestation. We performed whole mtDNA genome sequencing and provided genealogical and molecular genetic data on mutations and haplogroup background of LHON patients. Known “primary” pathogenic mtDNA mutations (MITOMAP) were found in 32 families: m.11778G>A represents 53.10% (17/32), m.3460G>A—21.90% (7/32), m.14484T>C–18.75% (6/32), and rare m.10663T>C and m.3635G>A represent 6.25% (2/32). We describe potentially pathogenic m.4659G>A in one subject without known pathogenic mutations, and potentially pathogenic m.6261G>A, m.8412T>C, m.8551T>C, m.9444C>T, m.9921G>A, and m.15077G>A in families with known pathogenic mutations confirmed. We suppose these mutations could contribute to the pathogenesis of optic neuropathy development. Our results indicate that haplogroup affiliation and mutational spectrum of the Western Siberian LHON cohort substantially deviate from those of European populations.

Leber's Hereditary Optic Neuropathy as a Cause of Severe Visual Loss in Childhood

PEDIATRICS ◽  
1993 ◽  
Vol 91 (5) ◽  
pp. 988-989
Author(s):  
C. M. MOORMAN ◽  
J. S. ELSTON ◽  
P. MATTHEWS
Keyword(s):  
Optic Neuropathy ◽  
Visual Loss ◽  
Age Of Onset ◽  
Transmitted Disease ◽  
Point Mutations ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Leber's Hereditary Optic Neuropathy ◽  
Severe Visual Loss ◽  
Sporadic Cases ◽  
Hereditary Optic Neuropathy

Leber's hereditary optic neuropathy (LHON) is a rare, maternally transmitted disease that most commonly causes acute or subacute visual loss in young men, typically between the ages of 17 and 24 years (although perhaps 14% of affected individuals are women), which may be associated with systemic disorders, eg, cardiac dysrhythmias and neurologic problems.1 Onset is usually asymmetric, but intervals between involvement of the two eyes are usually less than a few months. A definitive diagnosis rested on a family history, age of onset, and the characteristic circumpapillary microangiopathy of the optic disc in the acute phase. However, recent demonstration of point mutations of mitochondrial DNA in affected individuals means that confirmation of the diagnosis can now be obtained in atypical or sporadic cases.2

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