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

A novel mtDNA point mutation was detected in the tRNAleu(CUN) gene (G to A at position 12315) in a sporadic patient with chronic progressive external ophthalmoplegia, ptosis, limb weakness, sensorineural hearing loss and a pigmentary retinopathy. The mutation disrupts base pairing in the T psi C stem at a site which has been conserved throughout evolution. Although the other mtDNA tRNAleu gene (UUR) is a hotspot for mutation, this is the first pathogenic mutation to be reported in the gene coding for tRNAleu(CUN). MtDNAs carrying the mutation constituted 94% of total mtDNAs in two separate muscle biopsies. Single fibre analysis showed that skeletal muscle fibres without detectable cytochrome c oxidase activity (COX-ve fibres) contained predominantly mutant mtDNAs (93-98%) while fibres with apparently normal COX activity had up to 90% mutant mtDNAs, demonstrating that the G12315A mutation is functionally recessive. Immunofluorescence studies with specific antibodies to mtDNA- or nuclear-encoded subunits of COX were consistent with a defect in mitochondrial protein translation. The mutation was not present in blood cells or cultured fibroblasts and surprisingly, it could not be detected in satellite cells cultured from the patient's muscle. This pattern, which may by typical of patients who have inherited new germline pathogenic mtDNA mutations, possibly reflects loss of the mutation by random genetic drift in mitotic tissues and proliferation of mitochondria containing the mutant mtDNA in post-mitotic cells. The absence of mtDNA carrying the mutation in satellite cells suggests that regeneration of skeletal muscle fibres from satellite cells could restore a wild-type mtDNA genotype and normal muscle function.
 ...
PMID:A novel heteroplasmic tRNAleu(CUN) mtDNA point mutation in a sporadic patient with mitochondrial encephalomyopathy segregates rapidly in skeletal muscle and suggests an approach to therapy. 892 13

The Kearns-Sayre (K-S) syndrome which includes the triad of progressive external ophthalmoplegia, pigment retinopathy, and disorder of cardiac conduction was first described in 1958. The mitochondria disorder is believed to be the cause of this syndrome. Involvement of the cardiac conduction system is the most importent prognostic factor in K-S syndrome. A 34-year-old male K-S syndrome patient, manifesting as ptosis and weakness of limbs since the age of 15 years, suffered from dizziness and weakness. Twelve-lead eletrocardiography (ECG) showed a 2:1 atrioventricular (AV) block with slow ventricular rate. Intermittent complete AV block, complete left bundle branch block and torsades de pointes were noted in Holter ECG. The electrophysiology study demonstrated prolonged HV interval (85 ms) on conduction beat and infra-His block on non-conduction beat. A VVIR mode of permanent pacemaker was implanted and the patient's condition was stable during this period of follow-up.
 ...
PMID:Atrioventricular block in Kearns-Sayre syndrome: a case report. 1155 73

The afferent and efferent visual pathways within the central nervous system are frequently involved in mitochondrial diseases. Neuro-ophthalmic signs figure prominently and may be the presenting or even sole manifestation of these disorders. The four most common neuro-ophthalmic abnormalities seen in mitochondrial disorders are bilateral optic neuropathy, ophthalmoplegia with ptosis, pigmentary retinopathy, and retrochiasmal visual loss.
 ...
PMID:Neuro-ophthalmology of mitochondrial diseases. 1164 18

A 74-year-old man with diabetes mellitus type II, retinopathy and polyneuropathy suffered from exophthalmus, ptosis and diplopia. Magnetic resonance imaging and computer tomography showed a space-occupying process in the right orbital apex. An extranasal ethmoidectomy accompanied by an orbitotomia revealed the presence of septated hyphae. Aspergillus fumigatus was grown from the tissue. After surgical removal of the fungal masses, therapy with amphotericin B (1 mg kg(-1) body weight) plus itraconazole (Sempera, 200 mg per day) over 6 weeks was initiated. Five months later the patient's condition deteriorated again, with vomiting, nausea and pain behind the right eye plus increasing exophthalmus. Antifungal therapy was started again with amphotericin B and 5-fluorocytosine. Neutropenia did not occur. The patient became somnolent and deteriorated, a meningitis was suggested. Aspergillus antigen (titre 1:2, Pastorex) was detected in liquor. Anti-Aspergillus antibodies were not detectable. Both the right eye and retrobulbar fungal masses were eradicated by means of an exenteratio bulbi et orbitae. However, renal insufficiency and an apallic syndrome developed and the patient died. At autopsy, a mycotic aneurysm of the arteria carotis interna dextra was detected. The mycotic vasculitis of this aneurysm had caused a rupture of the blood vessel followed by a massive subarachnoidal haemorrhage. In addition, severe mycotic sphenoidal sinusitis and aspergillosis of the right orbit were seen, which had led to a bifrontal meningitis.
 ...
PMID:Case report. Mycotic arteritis due to Aspergillus fumigatus in a diabetic with retrobulbar aspergillosis and mycotic meningitis. 1176 8

Three affected sibs in a consanguineous family with short stature, mental retardation, downslanting palpebral fissures, ptosis and polydactyly are described. There was no hypogonadism or pigmentary retinopathy. They were thin in childhood and while two of the postpubertal sibs have a stocky build none is obese. We propose that this could be a previously unreported autosomal recessive syndrome.
 ...
PMID:Mental retardation, ptosis and polydactyly: a new autosomal recessive syndrome? 1240 96

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.
 ...
PMID:POLG mutations in sporadic mitochondrial disorders with multiple mtDNA deletions. 1463 18

Kearns-Sayre syndrome (KSS) is a mitochondrial encephalomyopathy characterized by progressive external ophthalmoplegia (PEO), pigmentary retinopathy and onset before the age of 20 years. Cerebellar ataxia, as well as short stature and increased protein content in the cerebrospinal fluid, are frequent additional symptoms. A single large mitochondrial (mt) DNA deletion of 4,977 bp is the most common molecular defect in KSS. Recently, different mutations have also been associated with incomplete, KSS-like phenotypes. We describe the unusual clinical presentation of a patient carrying a novel 1,814-bp deletion of mtDNA. In contrast with typical KSS, the clinical picture of this patient did not include either palpebral ptosis or PEO and was dominated by an ataxic syndrome.
 ...
PMID:Unusual clinical presentation of a patient carrying a novel single 1.8 kb deletion of mitochondrial DNA. 1673

Kearns Sayre syndrome (KSS) is a mitochondrial disorder characterized by the emergence before age 20 of progressive external ophthalmoplegia, pigmentary retinopathy, together with other heterogeneous clinical manifestations, including cardiac conduction defects, muscle abnormalities and endocrinopathies. KSS is associated with large heteroplasmic deletions in mitochondrial DNA. We report the case of a 43-year-old woman, with diabetes mellitus as a first manifestation at age 19. Later, she exhibited bilateral ptosis and external ophthalmoplegia with progressive worsening. DNA analysis identified a large mitochondrial DNA (mtDNA) deletion, which confirmed the diagnosis of KSS. By reporting this case with diabetes mellitus as first manifestation, we aim at emphasizing problems of diagnosis in these subtypes of mitochondrial diabetes.
 ...
PMID:Kearns Sayre syndrome: an unusual form of mitochondrial diabetes. 1673 69

Adult-onset Still's disease is a multisystem inflammatory disorder of unknown etiology and is characterized by high, spiking fever, arthritis, evanescent maculopapular rash, myalgia, serositis, leukocytosis, and involvement of various organs including the eyes. The ocular manifestations have been described including orbital pseudotumor, ptosis, and diplopia with orbital pain but never Purtscher's-like retinopathy. We describe a 21-year-old male patient with adult-onset Still's disease who developed the Purtscher's-like retinopathy. To our knowledge, this is the first reported adult-onset Still's disease patient with Purtscher's-like retinopathy as the initial presentation.
 ...
PMID:Purtscher's-like retinopathy as an initial presentation of adult-onset Still's disease: a case report and review of the literature. 1690 Mar 1

The Kearns-Sayre syndrome is a neuromyopathic disorder associated with mitochondrial abnormalities and characterized by the triad of chronic external ophthalmoplegia, atypical pigmentary retinopathy, and progressive conduction system disorders. Ragged red muscle fibers that seem to contain an excess of altered mitochondria are observed. The disease affects both sexes alike, during the first or the second decade of life. The following manifestations are observed: central bilateral sensorineural deafness, pyramidal signs, ataxia, asymmetrical ptosis, external ophthalmoplegia, and progressive muscular weakness secondary to myopathy associated with a significant increase of proteins of cephalorachidian liquid. A variety of endocrinopathies may occur.
 ...
PMID:Kearns-Sayre syndrome: electro-vectorcardiographic evolution for left septal fascicular block of the his bundle. 1849 26


<< Previous 1 2 3 4 Next >>