Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the correlation of clinical symptoms and deletion of mitochondrial DNA (mtDNA) in CPEO, we examined brain MRI, lower limb SSEP and mtDNA in 19 patients (nine men, ten women) with CPEO averaging 44.9 years of age. Of these patients, three had typical Kearns-Sayre syndrome (KSS) as defined by the presence of the invariable triad of CPEO, retinitis pigmentosa and an onset before the age of 20, as well as at least one of the followings: heart conduction block, cerebellar ataxia and elevated CSF protein. One patient was diagnosed as having probable KSS because the symptoms had begun at the age of 33. All patients with typical and probable KSS had one or more of the following common manifestations: mental retardation or dementia, hearing loss, short stature, and endocrinological disorder. All other 15 patients had ocular myopathy with limb muscle weakness. Total DNA was isolated from 19 biopsied muscles, and analyzed by the methods of Southern blot hybridization and PCR. Thirteen patients has heteroplasmy with the deleted and normal mtDNA, and six patients who had ocular myopathy did not have mtDNA deletion. The age of onset in the patients with mtDNA deletion averaged 23.0 years of age, while that without mtDNA deletion averaged 39 years of age. All KSS and two ocular myopathy patients shared the common site in mtDNA deletion, while nine with ocular myopathy showed the different sizes of deletion ranging from 2.3 to 9.5 kb in the different sites. Brain MRI was obtained from 12 of the 19 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Chronic progressive external ophthalmoplegia (CPEO); mitochondrial DNA deletion, brain MRI and electrophysiological studies]. 176 62

A 19-year-old man with chronic progressive external ophthalmoplegia with deleted mitochondrial DNA was reported. Neurological examination revealed bilateral external ophthalmoplegia, hearing loss of sensorineural type, short stature, mental retardation, muscle atrophy and weakness in the proximal muscles. Lactate and pyruvate levels were elevated in both serum and cerebrospinal fluid (CSF). Protein concentration was slightly increased in CSF. Electromyogram showed myopathic changes on all the muscles examined. Ragged-red fibers were found in biopsied rectus femoris muscle, stained with modified Gomori trichrome. Scattered cytochrome c oxidase deficient fibers were encountered. The computed tomography of the brain showed mild cerebral and cerebellar atrophy without any abnormal calcification or hypo-lucency. Southern blot analysis of the mitochondrial DNA (mtDNA) extracted from the patient's muscle revealed mixed population of mtDNA, consisting of the normal one and partially deleted one. The size of the deletion was about 4.5-kilobase. The region included the sequences coding for at least four subunits of Complex I, one subunit of Complex IV, two subunits of Complex V and five tRNAs. There may be a "hot area" on the mitochondrial genome that is more prone to be deleted than other regions of mtDNA. Southern blot analysis is usefull for the diagnosis of KSS or CPEO.
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PMID:[Chronic progressive external ophthalmoplegia (CPEO) with deleted mitochondrial DNA]. 259 47

Chronic progressive external ophthalmoplegia (CPEO) is one of the most common mitochondrial disorders. It is characterized by bilateral, slowly progressing loss of extraocular muscle mobility, orbicularis oculi weakness, ptosis, and other neuromuscular symptoms, which are caused by the accumulation of multiple mitochondrial DNA (mtDNA) deletions. Many mutations in different nuclear genes, such as POLG1, POLG2, ANT1, and others, have been described as causing autosomal-inherited CPEO with multiple mtDNA deletions. Most causative genes are involved in mtDNA replication impairment. Here, we report a family with CPEO-like symptoms characterized by multiple muscle mtDNA deletions, ptosis, diabetes, hearing loss, mental retardation, and emotional instability. We performed genetic analyses to identify nuclear gene mutations in the family. DNA from the proband was analyzed by whole-exome sequencing. In addition to possible pathogenic mutations, rare variants were prioritized for gene-functional phenotype interpretation. We found possible pathogenetic mutations in the PRIMPOL, BRCA1, CPT2, and GJB2 genes, and functional polymorphisms in the CARD8, and MEFV genes. Multiple functional polymorphisms and possible pathogenic mutations may contribute to mitochondrial-disease-like phenotypes in a composite manner.
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PMID:A PRIMPOL mutation and variants in multiple genes may contribute to phenotypes in a familial case with chronic progressive external ophthalmoplegia symptoms. 3134 95