Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a prospective randomized and double-blind cross-over study, a new antiemetic regimen consisting of betamethasone (1 x 8 mg) and dixyrazine (a phenothiazine derivative) (4 x 10 mg) was compared with a standard high-dose metoclopramide (4 x 1 mg/kg) schedule for antiemetic treatment in doxorubicin and cisplatin chemotherapy. 100 consecutive patients (62 without prior experience of chemotherapy and 38 with prior experience) entered the study and were followed during 1-4 courses of chemotherapy. Effect and side effect parameters were recorded on questionnaires for patients and nurses using the visual analog scale for quantification. The correlation between the two ways of recording (self-scoring versus recording by nursing staff) was very high, both for effect variables (nausea and vomiting) and the adverse reactions (sedation and extrapyramidal reactions). The median number of courses per patient was 3.0 (range 1-4) and altogether 299 courses were studied. Full emetic protection was achieved in 58% with betamethasone-dixyrazine and in 34% with high-dose metoclopramide regardless of prior patient experience or the cytostatic agents administered. With doxorubicin regimens, betamethasone-dixyrazine gave full protection in 80% compared to 40% for metoclopramide. Cisplatin regimens were a greater challenge and protection against nausea and vomiting was achieved only in 27% with betamethasone-dixyrazine and in 18% with metoclopramide. Adverse reactions were a significant problem with metoclopramide: restlessness 33%, akathisia 19%, parkinsonism 16%, and acute dystonia 3%. Sedation was the same with the two regimens (80%).
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PMID:Betamethasone-dixyrazine combination versus high-dose metoclopramide as antiemetic treatment in doxorubicin and cisplatin chemotherapy. 276 89

In 1960, progressive sensorineural deafness (McKusick 304,700, DFN-1) was shown to be X-linked based on a description of a large Norwegian pedigree. More recently, it was shown that this original DFN-1 family represented a new type of recessive neurodegenerative syndrome characterized by postlingual progressive sensorineural deafness as the first presenting symptom in early childhood, followed by progressive dystonia, spasticity, dysphagia, mental deterioration, paranoia and cortical blindness. This new disorder, termed Mohr-Tranebjaerg syndrome (referred to here as DFN-1/MTS) was mapped to the Xq21.3-Xq22 region2. Using positional information from a patient with a 21-kb deletion in chromosome Xq22 and sensorineural deafness along with dystonia, we characterized a novel transcript lying within the deletion as a candidate for this complex syndrome. We now report small deletions in this candidate gene in the original DFN-1/MTS family, and in a family with deafness, dystonia and mental deficiency but not blindness. This gene, named DDP (deafness/ dystonia peptide), shows high levels of expression in fetal and adult brain. The DDP protein demonstrates striking similarity to a predicted Schizosaccharomyces pombe protein of no known function. Thus, is it likely that the DDP gene encodes an evolutionarily conserved novel polypeptide necessary for normal human neurological development.
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PMID:A novel X-linked gene, DDP, shows mutations in families with deafness (DFN-1), dystonia, mental deficiency and blindness. 884 Nov 89

The human deafness dystonia syndrome results from the mutation of a protein (DDP) of unknown function. We show now that DDP is a mitochondrial protein and similar to five small proteins (Tim8p, Tim9p, Tim10p, Tim12p, and Tim13p) of the yeast mitochondrial intermembrane space. Tim9p, Tim10p, and Tim12p mediate the import of metabolite transporters from the cytoplasm into the mitochondrial inner membrane and interact structurally and functionally with Tim8p and Tim13p. DDP is most similar to Tim8p. Tim8p exists as a soluble 70-kDa complex with Tim13p and Tim9p, and deletion of Tim8p is synthetically lethal with a conditional mutation in Tim10p. The deafness dystonia syndrome thus is a novel type of mitochondrial disease that probably is caused by a defective mitochondrial protein-import system.
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PMID:Human deafness dystonia syndrome is a mitochondrial disease. 1005 50

Primary dystonias are movement disorders with dystonia as a major symptom. They are frequently inherited as Mendelian traits. There are at least eight clinically distinct autosomal dominant and two X-linked recessive forms. In addition, pedigree analyses suggest the occurrence of an autosomal recessive variant. The clinical classification is increasingly being replaced by a genetic one. To date gene loci have been identified in at least six autosomal dominant forms, i.e., in idiopathic torsion dystonia (9q34), focal dystonia (18p), adult-onset idiopathic torsion dystonia of mixed type (8p21-q22), dopa-responsive dystonia (14q22.1-q22.2), and paroxysmal dystonic choreoathetosis (2q25-q33; 1p21-p13.3). Gene loci in the X-linked recessive forms have been assigned to Xq13.1 in the X-linked dystonia parkinsonism syndrome and to Xq22 in X-linked sensorineural deafness, dystonia, and mental retardation. The disease genes have been identified in two autosomal dominant forms and in one X-linked recessive form. Mutations in a gene coding for an ATP-binding protein were detected in idiopathic torsion dystonia (DYT1), and the GTP cyclohydrolase 1 gene is mutated in dopa-responsive dystonia (DYT5). In sensorineural deafness, dystonia, and mental retardation, mutations were found in the gene DDP coding for a polypeptide of unknown function. This article reviews the clinical and molecular genetics of primary dystonias, critically discusses present findings, and proposes referring to the known forms, most of which can be distinguished by genetic criteria, as dystonias 1-12.
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PMID:Clinical and molecular genetics of primary dystonias. 1073 19

We report the first de novo mutation in the DDP gene in a Dutch 11-year-old boy with deafness and dystonia. Previously reported mutations in the DDP gene have all been frameshifts/nonsense mutations or deletion of the entire gene as part of a larger deletion encompassing the BTK gene. The clinical presentation was uniformly characterised by sensorineural hearing loss, dystonia, mental deterioration, paranoid psychotic features, and optic atrophy, indicating progressive neurodegeneration. Our report illustrates that de novo mutations occur and that a missense mutation, C66W, may cause an equally severe clinical picture. The diagnosis of sensorineural hearing impairment associated with neurologic and visual disability in a male, therefore, should encourage the search for mutations in the DDP gene, even in sporadic cases. The association of deafness-dystonia syndrome with a missense mutation provides valuable information for in vitro investigations of the functional properties of the deafness-dystonia peptide which was recently shown to be the human homolog of a yeast protein, Tim8p, belonging to a family of small Tim proteins involved in intermembrane protein transport in mitochondria.
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PMID:A de novo missense mutation in a critical domain of the X-linked DDP gene causes the typical deafness-dystonia-optic atrophy syndrome. 1087 69

The Mohr-Tranebjaerg-Jensen deafness-dystonia-optic atrophy protein DDP/TIMM8a is translated on cytoplasmic ribosomes but targeted ultimately to the mitochondrial intermembrane space, where it is involved in mitochondrial protein import. STAM1 is a cytoplasmic signal-transducing adaptor molecule implicated in cytokine signaling. We report here a direct interaction between DDP and STAM1, identified by yeast two-hybrid screening and confirmed by co-immunoprecipitation, fusion protein "pull downs," and nuclear redistribution assays. DDP coordinates Zn(2+), and Zn(2+) was found to stimulate the DDP-STAM1 interaction in vitro. Endogenous STAM1 localizes predominantly to early endosomes, and we found no evidence that STAM1 is imported into mitochondria in vitro. Thus, the DDP-STAM1 interaction likely occurs in the cytoplasm or at the mitochondrial outer membrane. The DDP-STAM1 interaction requires a coiled-coil region in STAM1 that overlaps with the immunoreceptor tyrosine-based activation motif (ITAM), a region previously shown to be important for interaction with Jak2/3 and hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs). Thus, DDP binding may alter the interactions of STAM1 with several cytoplasmic proteins involved in cell signaling and endosomal trafficking.
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PMID:Interaction of the deafness-dystonia protein DDP/TIMM8a with the signal transduction adaptor molecule STAM1. 1274 81