线粒体疾病mitochondrialdiseases

Medical Genetics
If there is a mutation in a mitochondrial gene, it is passed from a mother to all of her children; sons will not pass it on, but daughters will pass it on to all of their children, and so on.
Medical Genetics
There are many forms of mitochondrial disease. Mitochondrial disease presents very differently from individual to individual.
Medical Genetics
• Disease signs especiBaidu Nhomakorabeally manifest in
– Tissues with a high energy expenditure: Dependent on oxidative metabolism
– Specific tissues: Brain, Heart & Muscle
Medical Genetics
Mitotic segregation
– % of mutant mtDNAs in daughter cells can shift at cell division
– Produces rapid changes of genotype that may lead to crossing of threshold
Medical Genetics
3. LHON
LHON = Leber's; Hereditary; Optic; Neuropathy
Medical Genetics
Genetic-Clinical correlations: Maternal Inheritance
• Recurrence risks: Brother 30%; Sister 8%; Nephew 46%; Niece 10%; Male cousin 31%; Female cousin 6%
Medical Genetics
13 线粒体疾病
mitochondrial diseases
Medical Genetics
Mutations (changes) in the mitochondrial chromosome are responsible for a number of disorders.
Medical Genetics
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.
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.
Medical Genetics
Medical Genetics
Threshold effect
• % of mutant mtDNAs must be above a threshold to produce clinical manifestations
• % of mutant mtDNAs needed to cause cell dysfunction varies according to tissue oxidative requirements
• 40% of patients with commonest mutation (G11778A) have negative family history
• Large families with maternal inheritance: G11778 & T14484C mutations
Medical Genetics
The incidence about 1:3000-4000 individuals in the US.
Medical Genetics
Characteristics
Unlike nuclear genes, which are inherited from both parents, mitochondrial genes are inherited only from the mother.
Medical Genetics
Clinical features (General)
Male predominance:No relation to any X-linked genes
In mammals, 99.99% of mitochondrial DNA (mtDNA) is inherited from the mother. This is because the sperm carries its mitochondria around a portion of its tail and has only about 100 mitochondria compared to 100,000 in the oocyte.
Medical Genetics
Mutations (General)
– 3 Mutations account for 96% of cases
• All in Complex I genes • Mutations: G11778A (69%), G3460A (13%),
T14484C (14%)