遗传学精品教学（南京大学）Chapter 10 Mitochondrial genetics-2.pptVIP

* * Basal ganglia calcification, cerebellar atrophy, increased lactate; a CT image of a person diagnosed with MELAS * Oculo-cranio-somatic: 眼-腔-体 * ptosis上睑下垂 * * Mitochondrial disorder Mitochondrial Genetics - 2 * * LHON MERRF MELAS NARP KSS Mitochondrial disease ---due to mitochondrial DNA mutation ★ * * Leber Hereditary optic neuropathy (LHON) (Leber 遗传性视神经病) First recognized mt disorder 11778 G to A, 3460 G to A and 14484 T to C, respectively in the ND4, ND1 and ND6 subunit genes of complex I * * Signs symptoms an acute onset of visual loss --- first in one eye, a few weeks to months later in the other. --- Onset is usually young adulthood, although age range from 8-60y. --- very severe optic atrophy and permanent decrease of visual acuity. * * Genetics Mutations in the MT-ND1, MT-ND4, MT-ND4L, and MT-ND6 genes The genes code for the NADH dehydrogenase protein involved in the normal mitochondrial function of oxidative phosphorylation. * * Epidemiology 1:9000 in Northern Europe 1:30,000 to 1:50,000 in Europe ND4 G11778A mutation with 70% of European cases; 90% of Asian cases ND6 T14484C mutation for 86% of LHON cases in Quebec, Canada 50 percent of males with a mutation and 85 percent of females with a mutation never experience vision loss or related medical problems ---Heteroplasmy, X-chromosome, haplogroup, …… * * Pathophysiology Degeneration in the retinal ganglion cell (RGC) layer especially the maculopapillary bundle. Impaired glutamate transport Increased reactive oxygen species (ROS) causing apoptosis of retinal ganglion cells. SOD2 and glutathione rescue LHON RGC from apoptotic death. * * Diagnosis management Without a known family history of LHON the diagnosis is difficult and usually requires a neuro-ophthalmological evaluation and/or blood testing for DNA assessment There is no accepted treatment, but the proposal for this disease Genetic counselling, avoid nerve toxin * * MERRF: myoclonic epilepsy and ragged-red fiber