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)

Mitochondrial dysfunction has been implicated in the pathogenesis of sporadic, idiopathic Parkinson disease. In some cases, mitochondrial DNA primary genetic abnormalities, or more commonly, secondary rearrangements due to polymerase gamma (POLG1) gene mutation, can directly cause parkinsonism. The case of a Parkinson disease patient with some signs or symptoms suggestive of mitochondrial disease (i.e., ptosis, myopathy, neuropathy) is a relatively common event in the neurological practice. Mitochondrial parkinsonisms do not have distinctive features allowing an immediate diagnosis, and a negative family history does not rule out a possible diagnosis of mitochondrial disorder. In this article, we do not revise the mitochondrial hypothesis of sporadic, idiopathic Parkinson disease, extensively discussed elsewhere, but we review POLG1-related parkinsonism and other well-defined forms of "mitochondrial parkinsonisms", with mtDNA mutations or rearrangements. Lastly, we try to introduce a possible diagnostic approach for patients with parkinsonism and suspected mitochondrial disorder.
 ...
PMID:POLG1-related and other "mitochondrial Parkinsonisms": an overview. 2122 44

Mutations in the POLG gene have emerged as one of the most common causes of inherited mitochondrial diseases in children and adults. This study sequenced the exons and flanking intronic regions of the POLG gene from 2697 unrelated patients with clinical presentations suggestive of POLG deficiency. Informative mutations have been identified in 136 unrelated individuals (5%), including 92 patients with two recessive pathogenic alleles and three patients harbouring a dominant mutation. Twenty-four novel recessive mutations and a novel possible dominant mutation, p.Y951N, were identified. All missense mutations occurred at evolutionarily conserved amino acids within functionally important regions identified by molecular modelling analyses. Oligonucleotide array comparative genomic hybridisation analyses performed on DNA samples from 81 patients with one mutant POLG allele identified a large intragenic deletion in only one patient, suggesting that large deletions in POLG are rare. The 92 patients with two mutant alleles exhibited a broad spectrum of disease. Almost all patients in all age groups had some degree of neuropathy. Seizures, hepatopathy, and lactic acidaemia were predominant in younger patients. By comparison, patients who developed symptoms in adulthood had a higher percentage of myopathy, sensory ataxia, and chronic progressive external ophthalmoplegia (CPEO)/ptosis. In conclusion, POLG mutations account for a broad clinical spectrum of mitochondrial disorders. Sequence analysis of the POLG gene should be considered as a part of routine screening for mitochondrial disorders, even in the absence of apparent mitochondrial DNA abnormalities.
 ...
PMID:Mitochondrial DNA polymerase gamma mutations: an ever expanding molecular and clinical spectrum. 2188 Aug 68

The aim of the study was to determine the prevalence of MNGIE-like phenotype in patients with recessive POLG1 mutations. Mutations in the POLG1 gene, which encodes for the catalytic subunit of the mitochondrial DNA polymerase gamma essential for mitochondrial DNA replication, cause a wide spectrum of mitochondrial disorders. Common phenotypes associated with POLG1 mutations include Alpers syndrome, ataxia-neuropathy syndrome, and progressive external ophthalmoplegia (PEO). Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder characterized by severe gastrointestinal dysmotility, cachexia, PEO and/or ptosis, peripheral neuropathy, and leukoencephalopathy. MNGIE is caused by TYMP mutations. Rare cases of MNGIE-like phenotype have been linked to RRM2B mutations. Recently, POLG1 mutations were identified in a family with clinical features of MNGIE but no leukoencephalopathy. The coding regions and exon-intron boundaries of POLG1 were sequence analyzed in patients suspected of POLG1 related disorders. Clinical features of 92 unrelated patients with two pathogenic POLG1 alleles were carefully reviewed. Three patients, accounting for 3.3% of all patients with two pathogenic POLG1 mutations, were found to have clinical features consistent with MNGIE but no leukoencephalopathy. Patient 1 carries p.W748S and p.R953C; patient 2 is homozygous for p.W748S, and patient 3 is homozygous for p.A467T. In addition, patient 2 has a similarly affected sibling with the same POLG1 genotype. POLG1 mutations may cause MNGIE-like syndrome, but the lack of leukoencephalopathy and the normal plasma thymidine favor POLG1 mutations as responsible molecular defect.
 ...
PMID:Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)-like phenotype: an expanded clinical spectrum of POLG1 mutations. 2199 18

We report an early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous family characterized clinically by lower extremity spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. Whole-exome sequencing identified a homozygous missense mutation (c.1847G>A; p.Y616C) in AFG3L2, encoding a subunit of an m-AAA protease. m-AAA proteases reside in the mitochondrial inner membrane and are responsible for removal of damaged or misfolded proteins and proteolytic activation of essential mitochondrial proteins. AFG3L2 forms either a homo-oligomeric isoenzyme or a hetero-oligomeric complex with paraplegin, a homologous protein mutated in hereditary spastic paraplegia type 7 (SPG7). Heterozygous loss-of-function mutations in AFG3L2 cause autosomal-dominant spinocerebellar ataxia type 28 (SCA28), a disorder whose phenotype is strikingly different from that of our patients. As defined in yeast complementation assays, the AFG3L2(Y616C) gene product is a hypomorphic variant that exhibited oligomerization defects in yeast as well as in patient fibroblasts. Specifically, the formation of AFG3L2(Y616C) complexes was impaired, both with itself and to a greater extent with paraplegin. This produced an early-onset clinical syndrome that combines the severe phenotypes of SPG7 and SCA28, in additional to other "mitochondrial" features such as oculomotor apraxia, extrapyramidal dysfunction, and myoclonic epilepsy. These findings expand the phenotype associated with AFG3L2 mutations and suggest that AFG3L2-related disease should be considered in the differential diagnosis of spastic ataxias.
 ...
PMID:Whole-exome sequencing identifies homozygous AFG3L2 mutations in a spastic ataxia-neuropathy syndrome linked to mitochondrial m-AAA proteases. 2202 84

We report a case of unilateral mydriasis associated with sphenoid sinusitis and mucocele in a child. An 11-year-old girl with a history of unilateral mydriasis was referred for ophthalmologic examination. She complained of a mild headache over the past four days. The right pupil was dilated and nonreactive to light. The left pupil was normal and reactive. There was no ptosis or other focal neurological deficit. She was orthotropic. Visual acuity in both eyes, ocular motility and fundi were normal. Magnetic resonance imaging (MRI) showed a sphenoid sinus mucocele with sphenoiditis. The diagnosis was partial third nerve palsy without ophthalmoplegia. Treatment with antibiotics was initiated and led to complete resolution of the mydriasis. Sphenoid sinus mucoceles are relatively rare. Failure to diagnose and treat can lead to serious neurologic sequellae such as third nerve palsy, compressive optic neuropathy, cavernous sinus thrombosis, meningitis or brain abscess. Head imaging by reconstructed CT and MRI can lead to the diagnosis of mucocele. Isolated unilateral mydriasis as a sign of third nerve palsy may be caused by a slowly enlarging lesion. In a child with isolated unilateral mydriasis, head MRI should be performed to rule out a compressive lesion of the oculomotor nerve.
 ...
PMID:[Unilateral isolated partial third nerve palsy and sphenoiditis in a child: A case report]. 2247 36

Idiopathic orbital inflammatory syndrome (IOIS) is a nonspecific inflammation of orbital tissue. As it is a diagnosis of exclusion, systemic testing and, at times biopsy, is utilized to rule out other inflammatory etiologies. Since some inflammatory etiologies that masquerade as typical IOIS can be vision or life threatening, it is important to consider these diagnoses. Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune process that can affect the eye and visual system in 20% of individuals. In this idiopathic process, the deposition of pathogenic autoantibodies and immune complexes damage tissues and cells. Some common ocular manifestations of SLE include keratoconjunctivitis sicca, periocular skin lesions, orbital inflammation, retinal hemorrhages and vasculitis, retinal vaso-occlusive disease, iritis, scleritis, optic neuritis and optic neuropathy. One rare clinical entity in the SLE spectrum is panniculitis, also known as lupus erythematosus profundus (LEP), which is a nodular inflammation of adipose tissue. Panniculitis involving orbital structures as the primary presenting symptom of SLE is quite unusual and has only rarely been previously reported in the literature and has not been reported presenting as IOIS. This uncommon presentation can make the diagnosis more difficult. We describe a patient who had presented with ptosis evolving to orbital inflammation, which was consistent with IOIS by laboratory and histologic examinations. The patient later developed extensive panniculitis and a final diagnosis of LEP was made.
 ...
PMID:Lupus erythematosus profundus masquerading as idiopathic orbital inflammatory syndrome. 2255 72

Sudden painless loss of vision is an ophthalmologic and a medical emergency resulting from various causes such as occlusion of retinal artery or vein, macular or vitreous haemorrhages, retinal detachment, and anterior and posterior ischaemic optic neuropathy. We report a 48-year-old woman presenting with right monocular blindness due to branch retinal artery occlusion whose vision recovered due to timely paracentesis coupled with treatment with adequate antiplatelet agents and anticoagulants. The patient had transient diplopia and ptosis despite adequate antiplatelet agents and anticoagulants. Thorough search for aetiology revealed the underlying cause to be aortoarteritis. Aortoarteritis is a rare disease, and ocular involvement occurs late in the disease. We review ophthalmologic manifestation of aortoarteritis and diagnostic utilities of various modalities for aortoarteritis.
 ...
PMID:Sudden mono-ocular blindness with recurrent transient diplopia and ptosis in a middle-aged woman. 2270 Apr 85

Mutations in POLG1 are an important cause of human mitochondrial disease. We describe a woman who presented with bilateral ptosis and external ophthalmoplegia at 64 years of age. Neurological examination revealed symptoms of diffuse encephalopathy. The symptoms were progressive and at 67 years she was severely cognitively impaired, had severe bilateral ptosis and complete external ophthalmoplegia. Frequent cytochrome c oxidase-negative fibres were detected in muscle. Electrophysiological examination revealed myopathic changes and axonal neuropathy. Standard laboratory tests were normal. Brain CT showed general, moderate cortical atrophy. Molecular analysis of muscle DNA revealed multiple mitochondrial DNA deletions. Sequencing of the entire POLG1 gene revealed two changes c.2993C>T (p.998S>L) and c.3550G>C (p.1184D>H). Both mutations are previously unreported and confirmed to be compound heterozygous. Late-onset progressive external ophthalmoplegia with severe encephalopathy is an unusual combination in patients with POLG1 mutations. POLG-associated disease should be considered in any patient with unexplained or unusual neurological features.
 ...
PMID:Novel POLG1 mutations in a patient with adult-onset progressive external ophthalmoplegia and encephalopathy. 2277 64

An 80-year-old Caucasian woman had been diagnosed with right herpes zoster ophthalmicus 2 ½ weeks before presentation to our department. Ten days after stopping oral aciclovir, she presented with periorbital pain, visual loss, ptosis and complete ophthalmoplegia. On examination, visual acuity in her right eye was hand movements, with a relative afferent pupillary defect and 2 mm proptosis. MRI demonstrated contrast enhancement within the orbit extending into the apex, suggestive of an inflammatory process. Oral treatment was started with oral aciclovir and corticosteroids for 2 months, when she had resolution of the optic neuropathy and ophthalmoplegia. Vision recovered to 6/9 and repeat neuroimaging revealed regression of the inflammatory process.
 ...
PMID:Ophthalmoplegia secondary to herpes zoster ophthalmicus. 2279 18

A 3 1/2-year-old boy accidentally rode a bike into a shrubbery 1 day before he was presented at the clinic. He exhibited a hematoma of the right eyelid with ptosis without any obvious further injuries or visual complaints; however, a detailed examination revealed a profound loss of visual acuity of the right eye resulting from a serious traumatic optic neuropathy after being accidentally pierced by a twig through the left nostril.
 ...
PMID:[Hematoma of the eye: there's more to this than meets the eye!]. 2305 36


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>