Now a day the researchers still continue to determine whether genetic factors are the leading cause of Alzheimer disease (AD). Mutations of one in three genes (PSEN1, PSEN2, and APP) were identified causes of early AD. However, the percentage of patients with early AD is small. Although there wasn’t any genetic factors directly related to late-onset AD, in the last decades, genes of some risk factors leaded to this disease were determined more and more, especially genes caused vascular diseases. APOE was considered as highest risk factors for both of AD and vascular diseases. The risk factors of gene must be explained and put into the context of closed relations to the environment, nationality, geography and territory.
Dementia, Diagnosis , Molecular Biology

PURPOSE: Myoclonic epilepsy with ragged red fiber (MERRF) syndrome is a disease of the mitochondrial encephalomyopathies, characterized by progressive myoclonus (action), epilepsy, cerebellar ataxia, intention tremor, muscle weakness, progressive dementia, sensorineural hearing loss and optic atrophy. Its inheritance is maternally inherited mitochondrial mutation, and its pathologic finding is characterized by ragged red fibers (RRF). Biochemically its defects are diverse. This study was undertaken to investigate the pattern of mitochondrial mutation and characterize the clinical features in Korean patients with MERRF. METHODS: We collected 3 clinically suspected MERRF patients from 2 Korean families who have progressive myoclonus, epilepsy, cerebellar ataxia, intention tremor, muscle weakness, progressive dementia etc. We reviewed their clinical findings, electrophysiologic studies, radiologic findings and pathologic findings, retrospectively. Of the 2 patients (case 1 and case 3) who had undergone muscle biopsy, case 1 showed RRF in modified Gomori trichrome staining, increased mitochondrial number and abnormal inclusion body in EM. To examine the pattern of mitochondrial mutation of these patients, molecular study was carried out in 3 patients, 2 mothers, 2 fathers, and 4 siblings. Their genomic DNAs were isolated from peripheral leukocytes, subsequent PCR-direct nucleotide sequencing and Ban II digestion were followed. RESULTS: All mutations in our cases were A to G point mutations in the tRNALys gene at position 8344. CONCLUSION: We confirmed clinically suspected MERRF patients as MERRF and their mothers and siblings as carriers, on the basis of molecular genetic analysis. This study suggests that the molecular genetic analysis can be utilized to diagnose MERRF patients easily and confirm carriers, especially at the presymptomatic stage before the characteristic pathologic changes appear.
Biopsy ; Cerebellar Ataxia ; Dementia ; Diagnosis* ; Digestion ; DNA ; Epilepsies, Myoclonic* ; Epilepsy ; Fathers ; Hearing Loss, Sensorineural ; Humans ; Inclusion Bodies ; Leukocytes ; MERRF Syndrome ; Mitochondrial Encephalomyopathies ; Molecular Biology* ; Mothers ; Muscle Weakness ; Myoclonus ; Optic Atrophy ; Point Mutation ; Retrospective Studies ; RNA, Transfer, Lys ; Siblings ; Tremor ; Wills

PURPOSE: Myoclonic epilepsy with ragged red fiber (MERRF) syndrome is a disease of the mitochondrial encephalomyopathies, characterized by progressive myoclonus (action), epilepsy, cerebellar ataxia, intention tremor, muscle weakness, progressive dementia, sensorineural hearing loss and optic atrophy. Its inheritance is maternally inherited mitochondrial mutation, and its pathologic finding is characterized by ragged red fibers (RRF). Biochemically its defects are diverse. This study was undertaken to investigate the pattern of mitochondrial mutation and characterize the clinical features in Korean patients with MERRF. METHODS: We collected 3 clinically suspected MERRF patients from 2 Korean families who have progressive myoclonus, epilepsy, cerebellar ataxia, intention tremor, muscle weakness, progressive dementia etc. We reviewed their clinical findings, electrophysiologic studies, radiologic findings and pathologic findings, retrospectively. Of the 2 patients (case 1 and case 3) who had undergone muscle biopsy, case 1 showed RRF in modified Gomori trichrome staining, increased mitochondrial number and abnormal inclusion body in EM. To examine the pattern of mitochondrial mutation of these patients, molecular study was carried out in 3 patients, 2 mothers, 2 fathers, and 4 siblings. Their genomic DNAs were isolated from peripheral leukocytes, subsequent PCR-direct nucleotide sequencing and Ban II digestion were followed. RESULTS: All mutations in our cases were A to G point mutations in the tRNALys gene at position 8344. CONCLUSION: We confirmed clinically suspected MERRF patients as MERRF and their mothers and siblings as carriers, on the basis of molecular genetic analysis. This study suggests that the molecular genetic analysis can be utilized to diagnose MERRF patients easily and confirm carriers, especially at the presymptomatic stage before the characteristic pathologic changes appear.
Biopsy ; Cerebellar Ataxia ; Dementia ; Diagnosis* ; Digestion ; DNA ; Epilepsies, Myoclonic* ; Epilepsy ; Fathers ; Hearing Loss, Sensorineural ; Humans ; Inclusion Bodies ; Leukocytes ; MERRF Syndrome ; Mitochondrial Encephalomyopathies ; Molecular Biology* ; Mothers ; Muscle Weakness ; Myoclonus ; Optic Atrophy ; Point Mutation ; Retrospective Studies ; RNA, Transfer, Lys ; Siblings ; Tremor ; Wills