Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033377 (prolapse)
 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The accumulation of multiple mitochondrial DNA (mtDNA) deletions in stable tissues is a distinctive feature of several autosomal disorders, characterized by Progressive External Ophthalmoplegia (PEO), ptosis, and proximal myopathy. At least three nuclear genes are responsible for these disorders: ANT1 and C10orf2 cause autosomal dominant PEO, while mutations of DNA polymerase gammaA (POLG1 or POLG) gene on chromosome 15q25 causes both autosomal dominant and recessive forms of PEO. To investigate the contribution of these genes to the sporadic cases of PEO with multiple mtDNA deletions, we studied 31 mitochondrial myopathy patients without any family history for the disorder: 23 had PEO with myopathy, with or without the additional features of pigmentary retinopathy, ataxia, neurosensorial hypoacusia and diabetes mellitus, 7 presented isolated myopathy and one a peripheral neuropathy with ptosis. In all patients Southern blot of muscle DNA showed multiple mtDNA deletions; screening for ANT1 and C10ORF2 genes was negative. POLG analysis revealed mutations in eight patients; in six of them the mutations were allelic, while two patients were heterozygous. Five mutations were new, namely one stop codon (c.2407C>T/p.R709X) and four missense mutations (c.1085G>C/p.G268A; c.1967G>A/p.R562Q; c.2702G>C/p.R807P; c.3076C>T/p.H932W). A high degree of conservation was observed for all the new missense mutations. Only patients presenting PEO as part of their clinical phenotype had POLG mutations, in seven of them together with myopathic signs and in one with a sensori-motor peripheral neuropathy.
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PMID:POLG mutations in sporadic mitochondrial disorders with multiple mtDNA deletions. 1463 18

Autosomal dominant progressive external ophthalmoplegia (adPEO) is a mitochondrial disorder caused by mutations in nuclear genes. Here we report the clinical and genetic features of adPEO in a Chinese family. All patients had gradual onset of ptosis, with or without ophthalmoplegia, around age 30. Thirteen patients had limb weakness around age 40. Eight patients developed dysphagia around age 50. Four patients died of cardiac abnormalities around age 60. Muscle biopsy of the proband indicated mitochondrial myopathy characterized by ragged-red fibers, cytochrome c oxidase-negative fibers, and multiple deletions of mitochondrial DNA. A heterozygous missense mutation of c.1342A>G in the C10orf2 gene resulting in the p.448N>D mutation in the protein was found in the proband and four other affected family members. In summary, we identified an adPEO family with a novel C10orf2 gene mutation that manifested an age-dependent phenotype. It suggests that greater attention must be paid to cardiac abnormalities in the late stages of this disease.
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PMID:Clinical phenotype of autosomal dominant progressive external ophthalmoplegia in a family with a novel mutation in the C10orf2 gene. 1970 78

We described a case of a patient with autosomal dominant progressive external ophthalmoplegia (PEO) who presented with the acute onset dysphagia, quadriparesis, ptosis and respiratory insufficiency following a cardiac procedure and mimicking a myasthenic crisis. A pathogenic mutation in the C10orf2 (PEO1) gene was confirmed. The unusual presentation of our patient contributes to expand the clinical phenotype of PEO1 mutations and reinforces the need to consider mitochondrial myopathy as differential diagnosis of myasthenia gravis even in the case of acute onset symptoms.
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PMID:Progressive external ophthalmoplegia (PEO) due to a mutation in the C10orf2 (PEO1) gene mimicking a myasthenic crisis. 2401 82