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)

Machado-Joseph disease, an autosomal dominant multisystem motor degeneration, has been described mainly in people of Portuguese descent. Our report documents the presence of Machado-Joseph disease in the Chinese population, based on the specific molecular marker of a CAG repeat array in the 3' end of the MJD gene. We screened 21 Chinese families with dominant spinocerebellar ataxia. The results showed that Machado-Joseph disease with CAG expansion accounted for 52% of families with autosomal dominant cerebellar ataxia in this series. The clinical characteristics, besides the well-documented cerebellar ataxia, dysarthria, nystagmus, corticospinal dysfunctions, a variable degree of facial muscle fasciculation, and proprioceptive loss, included loss of optokinetic nystagmus and autonomic nervous system dysfunction. The CAG repeat number in the MJD gene ranged from 14 to 39 among normal alleles, and from 63 to 81 among MJD alleles. There was a strong inverse correlation (gamma = -0.77) between number of CAG repeats and age at symptom onset, accounting for 60% of the variance of age at onset. A strong clinical anticipation of age at onset existed in successive generations. Mild instabilities of expanded CAG repeat numbers during meiotic transmission occurred, with no significant difference according to the gender of the transmitting parent. Finally, brain metabolism in Machado-Joseph disease, studied with positron emission tomography, was characterized by significant progressive regional hypometabolism in the occipital cortex, as well as the cerebellar hemispheres, vermis, and brainstem.
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PMID:Machado-Joseph disease: clinical, molecular, and metabolic characterization in Chinese kindreds. 912 1

We report here, for the first time, the case of a 41-year-old man with both Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3) and myotonic dystrophy type 1. The patient noted dysarthria at 14 years of age and unsteady gait at 30 years of age. Similar sized expansions of the CAG trinucleotide repeats in one allele of the ataxin-3 (ATXN3) gene were found in both the patient and his father, although in the other allele the length of the CAG repeats was shorter in the father compared with the patient. In the dystrophia myotonica protein kinase (DMPK) gene the CTG repeats were much more expanded in the patient compared with his father. Thus it is possible that, in the farther, the short CAG repeat in the non-expanded ATXN3 allele delayed the onset of cerebellar symptoms, and/or that the expanded CTG repeat in the DMPK gene in the patient accelerated the pathogenesis of MJD/SCA3.
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PMID:Machado-Joseph disease/SCA3 and myotonic dystrophy type 1 in a single patient. 1971 33

Hereditary spinocerebellar degenerations (SCD) are a group of neurodegenerative disorders characterized by slowly progressive ataxia associated with non-cerebellar neurological signs and symptoms. In the Japanese population, dominantly inherited SCDs are much more common than recessively inherited or X-linked SCDs. The most common dominantly inherited SCD in Japan, as well as in many other countries, is Machado-Joseph disease, also known as spinocerebellar ataxia type 3 (MJD/SCA3). MJD/SCA3 is frequently accompanied by non-cerebellar symptoms, including progressive external ophthalmoplegia, pyramidal signs, dystonia, rigidity, dysarthria, and distal muscle atrophies. SCA6 and SCA31 represent a pure cerebellar subtype of SCD, occasionally accompanied by non-cerebellar signs. Detailed medical history and neurological examination are important for clinicians to diagnose hereditary SCDs, although genetic testing can help confirm the diagnosis. Despite increasing understanding of the molecular mechanisms underlying these fatal diseases, preventive therapies are currently lacking.
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PMID:[Overview of Hereditary Spinocerebellar Ataxias in Japan]. 2881 72