Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a case of cystinuria and glutamic aciduria, presenting with progressive cerebellar manifestations. She had cerebellar type dysarthria and limb ataxia. Head MRI revealed cerebellar atrophy. Urinary amino acid analysis showed excessive excretion of glutamate and the dibasic amino acids (cystine, arginine, lysine, and ornithine). Cystine and glutamic acid are thought to be transported in a common membrane transport system. Reduction of glutamic acid and cystine in the cerebrospinal fluid was revealed. A relationship between cystinuria and cerebellar manifestation was discussed.
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PMID:Cerebellar ataxia with glutamic aciduria. 168 67

Two half-brothers and their mother had symptomatic pyruvate dehydrogenase complex deficiency. The infants had severe congenital lactic acidosis, seizures, and apneic spells and died at the ages 3 and 4 months. The mother was less symptomatic with mental retardation, truncal ataxia, and dysarthria. The residual pyruvate dehydrogenase activities in cultured skin fibroblasts from the 2 infants and their mother were 7, 15, and 10% of control values. Immunoblot analysis showed negligible amounts of E1 alpha and E1 beta subunits of the complex. Northern blot analysis for the E1 alpha subunit showed normal results. In the 2 sons, complementary DNA sequence analysis revealed a cytosine to thymine mutation in exon 4, resulting in a change of arginine 127 to tryptophan in the E1 alpha subunit. Restriction enzyme analysis of the polymerase chain reaction product representing exon 4 of the E1 alpha gene revealed that the mother was a heterozygotes. Complementary DNA restriction analysis and methylation analysis of the X chromosome DXS255 loci revealed skewed activation of the mutant allele, consistent with the deficient pyruvate dehydrogenase activity in the mother's fibroblasts. The milder maternal phenotype is consistent with variable X-inactivation patterns in different organs of female heterozygotes.
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PMID:Pyruvate dehydrogenase deficiency: molecular basis for intrafamilial heterogeneity. 802 67

Senataxin recently was identified as the mutated gene in ataxia-oculomotor apraxia 2, which is characterized by ataxia, oculomotor apraxia, and increased alpha-fetoprotein levels. In this study, we evaluated 24 ataxic patients from 10 French-Canadian families. All cases have a homogeneous phenotype consisting of a progressive ataxia appearing between 2 and 20 (mean age, 14.8) years of age with associated dysarthria, saccadic ocular pursuit, distal amyotrophy, sensory and motor neuropathy, and increased alpha-fetoprotein levels but absence of oculomotor apraxia. Linkage disequilibrium was observed with markers in the ataxia-oculomotor apraxia 2 locus on chromosome 9q34. We have identified four mutations in senataxin in the French-Canadian population including two novel missense mutations: the 5927T-->G mutation changes the leucine encoded by codon 1976 to an arginine in the helicase domain (L1976R), and the 193G-->A mutation changes a glutamic acid encoded by codon 65 into a lysine in the N-terminal domain of the protein (E65K). The common L1976R mutation is shared by 17 of 20 (85%) carrier chromosomes. The study of this large French-Canadian cohort better defines the phenotype of this ataxia and presents two novel mutations in senataxin including the more common founder mutation in the French-Canadian population.
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PMID:Mutations in senataxin responsible for Quebec cluster of ataxia with neuropathy. 1573 1

We reported a 31-year-old man with recurrent cerebral venous thrombosis caused by congenital protein C deficiency. He was diagnosed with cerebral venous thrombosis before 7 months. He was transferred to our hospital with numbness of right hand and right side of face, and dysarthria. The blood examination showed that his protein C antigen level and protein C activity were decreased than the lower limits of normal. Brain magnetic resonance venography showed poor visualization of the superior sagittal sinus and cortical veins. Genetic analysis revealed a single-base substitution (C>T) at the codon 811 (Arg to Trp) in the 9th exon portion of the protein C gene. Taking those results, he was diagnosed with recurrent cerebral venous thrombosis due to congenital protein C deficiency. Cerebral venous sinus thrombosis that occurred in the absence of an incidents of disease or internal history when there is a juvenile onset, a past history, or a family history, is suspected of congenital thrombophilia and needs blood tests and genetic tests.
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PMID:[A case of recurrent cerebral vein thrombosis with protein C gene mutation identified]. 3048 63