Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a family of mitochondrial myopathy which appeared to be interited as an autosomal dominant trait. The proband is a 58-year-old Japanese male, who presented with bilateral ptosis, chronic progressive ophthalmopletia, dysphagia, and atrophy of proximal muscles in the upper extremities. There was no cataract or retinal degeneration. Serum creatine kinase (CK) and lactic acid levels were normal. Cardiac evaluations were normal. Muscle biopsy revealed 7% of ragged red fibers. Cytochrome c oxidase activity in the muscle was decreased to 50% of the control value. PCR analysis of muscle mitochondrial DNA revealed 3 large-scale deletions in the non-D-loop regions, ranging in size from 4.2 kb to 5.2 kb. His father, three siblings, and the two children had symptoms similar to the proband. We have reviewed forty-five individuals from six families, including our family, who had mitochondrial myopathy with autosomal dominant inheritance. Frequent manifestations include chronic progressive ophtalmoplegia (91.2%), ptosis (95.6%), hearing loss (72.7%), dysphagia (60.0%), limb weakness (74.1%), and respiratory muscle weakness (75.0%). Interestingly, there is no individual with retinal degeneration or cardiac involvement. Serum CK and lactic acid levels may be elevated. CT of the head is normal. Muscle biopsy shows ragged red fibers and the frequency of cytochrome c oxidase-negative fibers ranges from 0 to 38%. Multiple large-scale deletions of mitochondrial DNA, ranging in size from 4.2 to 8.3 kb, are found in the muscle, all of which are located in the non-D-loop region of the mitochondrial DNA. The multiplicity of deletions may be one to the characteristic features of this form of mitochondrial myopathy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Mitochondrial myopathy with autosomal dominant inheritance--report of a family and review of the literature]. 831 87

Defects in apoptosis (programmed cell death) have recently emerged as being closely involved in the pathogenesis of most ocular diseases and, therefore, apoptosis is now a topic of exponential interest in ophthalmology. This review summarizes recent works on mechanisms of apoptosis, from its initiation and modulation to the switching-on of its execution machinery. Interactions of cell death with cell division programs to orchestrate ontogenesis, aging, and adult life and their alterations in human diseases are pointed out. Two main apoptotic signaling pathways are identified: a death receptor-dependent (extrinsic) pathway and a mitochondrion-dependent (intrinsic) pathway. Mitochondrion harbors both antiapoptotic (Bcl-2, Bcl-XL) and apoptotic factors (Smac/Diablo, Apaf-1, cytochrome c). Its permeability transition pore (mPTP) is the main trigger of cell suicide. The process of mPTP opening, in association with extrusion to cytoplasm of a variety of apoptotic factors, is shown. Cytochrome c is one of these apoptotic factors. When expelled to cytoplasm, this double-faced respiratory chain component assembles with two other modules, Apaf-1 and procaspase 9, to form a protein complex--the apoptosome--that starts apoptosis execution. Another respiratory chain component, the CoQ10, is believed to counteract mPTP opening. What makes apoptosis particularly exciting for medicine is that its dysfunctions play a central role in the pathogenesis of several human diseases. For instance, excesses of apoptosis lead to cell loss that accompanies neurodegenerative diseases, whereas genetically determined defects of apoptosis lead to the deregulated cell proliferation typical of cancer. A variety of ophthalmologic diseases, such as post-keratectomy haze, corneal lesions, cataract, glaucoma, senile maculopathies, and genetic ocular pathologies, that underlie apoptosis dysfunctions are treated in detail in the other reviews of this issue.
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PMID:The mechanisms of apoptosis in biology and medicine: a new focus for ophthalmology. 1274 72

Cytochrome c oxidase (COX) deficiency is one of the most common respiratory chain deficiencies. A woman was presented at the age of 18y with acute loss of consciousness, non-convulsive status epilepticus, slow neurological deterioration, transient cortical blindness, exercise intolerance, muscle weakness, hearing loss, cataract and cognitive decline. Muscle biopsy revealed ragged-red fibers, COX negative fibers and a significant decreased activity of complex IV in a homogenate. Using next generation massive parallel sequencing of the mtDNA, a novel heteroplasmic mutation was identified in MTCO1, m.7402delC, causing frameshift and a premature termination codon. Single fiber PCR showed co-segregation of high mutant load in COX negative fibers. Mutation in mitochondrially encoded complex IV subunits should be considered in mitochondrial encephalomyopathies and COX negative fibers after the common mtDNA mutations have been excluded.
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PMID:Mitochondrial encephalomyopathy with cytochrome c oxidase deficiency caused by a novel mutation in the MTCO1 gene. 2495 8