医学遗传学 13线粒体病eng v.pptVIP

13 线粒体疾病mitochondrial diseases; Mutations (changes) in the mitochondrial chromosome are responsible for a number of disorders. ; Mitochondrial disease is a chronic, genetic disorder that occurs when the mitochondria of the cell fails to produce enough energy for cell or organ function. ? ; The incidence about 1:3000-4000 individuals in the US. ? This is similar to the incidence of cystic fibrosis of caucasian births in the U.S. ; There are many forms of mitochondrial disease. Mitochondrial disease presents very differently from individual to individual. ; Mitochondrial disease is inherited in a number of different ways. There may be one individual in a family or many individuals affected over a number of generations. ;1. Biochemical Genetic abnormalities of mitochondrial function;;;;;;;;2. The Symptoms of Mitochondrial Disease;3. LHON ;;;Clinical features (General) Male predominance:No relation to any X-linked genes Onset :Midlife: Mean 30 years; Range 1 to 70 Visual loss Clinical features Painless Visual loss pattern Severity: May deteriorate to 20/200 or less Progression: Mean 4 months; Interval between eyes affected: ~ 2 months Tendency to recover depends on mutation Pupillary reactions: May be relatively spared for degree of visual loss Ocular pathology Other features: Some families Cardiac conduction defects; Spastic dystonia; Spastic paraparesis; Dystonia;;;;4. MERRF ;;;Clinical syndrome: CNS Myoclonus (60%) Epilepsy (45%) Cerebellar dysfunction: Ataxia Dementia Optic atrophy (20%) Polyneuropathy (20%) Distal sensory loss (large fiber modalities) Hearing loss (40%) Myopathy Short stature (10%) Lipomata (10%) ;;;5. MELAS ;;;;;;;;6. Kearns-Sayre Syndrome ;mtDNA mutation types Single large mtDNA deletion (2 to 8 kb) Most common mutation type (80%) Common deletions Most common: 4977 base pairs from 8488 to 13460; 13 base pair repeat at mutation break point Thai patients: 3558 bp del