The triad of bilateral optic atrophy, hearing deficit, peripheral neuropathy is knoun to be a rare disorder. The authors experienced eight patients in three generations of the same family with this triad of deficits. The disorder developed since their childhood and the course was slowly progressive. Nerve conduction study suggested peripheral neuropathy and sural nerve biopsy was compatible with demyelinating neuropathy, as there were reduction of myelinated nerve fibers in number and focal onion-bulb formation. The mode of inheritance of the family seems to be autosomal dominant, with relatively high penetrance. In many respects, the disorder resembles the cases reported by Sylvester(1958) and Iwashita et al.(1970). But still we do not know the exact etiology of this disorder.
Biopsy ; Deafness* ; Family Characteristics ; Hearing ; Humans ; Nerve Fibers, Myelinated ; Neural Conduction ; Optic Atrophies, Hereditary* ; Optic Atrophy ; Penetrance ; Peripheral Nervous System Diseases* ; Sural Nerve ; Wills

OBJECTIVETo investigate the effect of secondary mutations on Leber's hereditary optic neuropathy (LHON).

METHODSThree primary and 24 secondary mutations were identified in 4 Chinese families which included male offspring.

RESULTSAll of the four pedigrees carried classic LHON mutations at nucleotide (nt) 11778, and did not carry any point of 24 secondary mutations. Nevertheless many polymorphic points were found in the nearby fragments of these pedigrees, such as 5178, 5108, 3705, 3721, 13734, etc.

CONCLUSIONMale offspring sequences should be analyzed in pedigrees with LHON to avoid the influence of familial inheritance characteristic which mitochondrial DNA polymorphism carried. Existence of the "repair genes" may affect the development of LHON.

Adolescent ; Adult ; DNA Mutational Analysis ; DNA, Mitochondrial ; chemistry ; genetics ; Female ; Humans ; Male ; Mutation ; Optic Atrophies, Hereditary ; genetics ; Pedigree ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Young Adult

A 45-year-old Korean woman visited our hospital complaining of poor vision after carbon monoxide (CO) poisoning. We have confirmed the presence of a point mutation at position 11778 in the ND4 gene of mitochondrial DNA. This case suggests that CO poisoning may precipitate the clinical expression of Leber's hereditary optic neuropathy (LHON). To our knowledge, this would be the first case report of clinical expression of LHON precipitated by CO poisoning.
Carbon Monoxide/adverse effects ; Carbon Monoxide Poisoning/*complications ; DNA Damage ; DNA, Mitochondrial/genetics ; Female ; Humans ; Middle Aged ; Optic Atrophies, Hereditary/*etiology/genetics ; *Point Mutation ; Visual Acuity

Abnormalities, Multiple ; diagnosis ; genetics ; pathology ; Brain ; diagnostic imaging ; pathology ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Optic Atrophies, Hereditary ; diagnostic imaging ; pathology ; Radiography ; Septo-Optic Dysplasia ; diagnosis ; genetics ; pathology ; Septum Pellucidum ; diagnostic imaging ; pathology

OBJECTIVE: Mitochondrial dysfunction is a prominent and early feature of Alzheimer's disease (AD). The morphologic changes observed in the AD brain could be caused by a failure of mitochondrial fusion mechanisms. The aim of this study was to investigate whether genetic polymorphisms of two genes involved in mitochondrial fusion mechanisms, optic atrophy 1 (OPA1) and mitofusin 2 (MFN2), were associated with AD in the Korean population by analyzing genotypes and allele frequencies. METHODS: One coding single nucleotide polymorphism (SNP) in the MFN2, rs1042837, and two coding SNPs in the OPA1, rs7624750 and rs9851685, were compared between 165 patients with AD (83 men and 82 women, mean age 72.3±4.41) and 186 healthy control subjects (82 men and 104 women, mean age 76.5±5.98). RESULTS: Among these three SNPs, rs1042837 showed statistically significant differences in allele frequency, and genotype frequency in the co-dominant 1 model and in the dominant model. CONCLUSION: These results suggest that the rs1042837 polymorphism in MFN2 may be involved in the pathogenesis of AD.
Alzheimer Disease* ; Brain ; Clinical Coding ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Mitochondrial Dynamics ; Optic Atrophy, Autosomal Dominant ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide

No abstract available.
DNA, Mitochondrial ; Optic Atrophy, Hereditary, Leber* ; Optic Nerve Diseases*

OBJECTIVETo describe the clinical and genetic characteristics of a Chinese family affected with optic atrophy 1 (OPA1).

METHODSLinkage analysis and DNA sequencing as well as PCR/restriction fragment length polymorphism (RFLP) analysis were performed to identify the disease-causing mutation.

RESULTSA missense mutation, G401D in the OPA1 gene was identified, and the patients demonstrate inherited syndrome of optic atrophy and hearing loss.

CONCLUSIONThe present study demonstrates that a mutation in the OPA1 gene can cause optic atrophy in Chinese patients, and supports the notion that OPA1 mutation may lead to OPA1 combined with hearing loss.

Adult ; Base Sequence ; Child ; China ; Chromosomes, Human, Pair 3 ; genetics ; DNA Mutational Analysis ; Family Health ; Female ; GTP Phosphohydrolases ; genetics ; Hearing Loss ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Optic Atrophy, Autosomal Dominant ; genetics ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length

The Leber's hereditary optic neuropathy, which affects mainly males in the late teens or in the early twenties, is a rare inherited disorder characterized by bilateral rapid loss of central vision. Leber's disease undergoes like optic neuritis in acute stage, but in late stage it results in optic atrophy with severe impairment of visual acuity and absolute central scotoma. Recently the authors have experienced two cases of Leber's optic neuropathy in a family. We observed a patient whose visual acuity of right eye was 0.8 at first examination, but reduced to 0.04 by 2 months after onset in spite of medical treatment, So we described the characteristic clinical findings of Leber's disease with brief review of the literatures.
Adolescent ; Humans ; Male ; Optic Atrophy ; Optic Atrophy, Hereditary, Leber* ; Optic Neuritis ; Scotoma ; Siblings* ; Visual Acuity

The authors have experienced with three cases of Leber's hereditary optic atrophy one family which is a relatively rare condition characterized by acute or subacute failrure of central vision presenting as a retrobulbar neuritis or optic atrophy typically inypung males in late teens or in the early twenties, though the age range is very wide. The literature relating to Leber's hereditary optic atrophy was briefly reviewed.
Adolescent ; Humans ; Male ; Optic Atrophy ; Optic Atrophy, Hereditary, Leber* ; Optic Neuritis

Leber's hereditary optic neuropathy is caused by a single nucleotide change in the mitochondrial deoxynucleic acid(mtDNA) and accounts for 30% of bilateral optic atrophy of unknown etiology. The authors found 11778 mtDNA mutation in 12 patients and evaluated the clinical manifegtations. We confirmed various phenotypes exist in Leber's hereditary optic neuropathy in Korea.
DNA, Mitochondrial* ; Humans ; Korea ; Optic Atrophy ; Optic Atrophy, Hereditary, Leber* ; Phenotype