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

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

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

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