Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0008489 (chorea)
 2,102 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The McLeod syndrome is an X-linked disorder caused by mutations of the XK gene encoding the XK protein. The syndrome is characterized by absent Kx erythrocyte antigen, weak expression of Kell blood group system antigens, and acanthocytosis. In some allelic variants, elevated creatine kinase, myopathy, neurogenic muscle atrophy, and progressive chorea are found. We describe a family with a novel point mutation in the XK gene consisting of a C to T base transition at nucleotide position 977, introducing a stop codon. Among seven affected males, five manifested with psychiatric disorders such as depression, bipolar disorder, or personality disorder, but only two presented with chorea Positron emission tomography and magnetic resonance volumetry revealed reduced striatal 2-fluoro-2-deoxy-glucose (FDG) uptake and diminished volumes of the caudate nucleus and putamen that correlated with disease duration. In contrast, none of 12 female mutation carriers showed psychiatric or movement disorders. However, a semidominant effect of the mutation was suggested by erythrocyte and blood group mosaicism and reduced striatal FDG uptake without structural abnormalities. Therefore, patients with psychiatric signs or symptoms segregating in an X-linked trait should be examined for acanthocytosis and Kell/Kx blood group serology.
 ...
PMID:McLeod syndrome: a novel mutation, predominant psychiatric manifestations, and distinct striatal imaging findings. 1126 14

Understanding molecular genetical background of hereditary chorea has recently been progressed so far. Triplet repeat expansion diseases including, Huntington disease, in which CAG expansion has been identified in the IT-15 or Huntingtin gene, and Huntington disease like-2, in which CTG expansion in junctophilin-3 (JPH3) gene occurs, causes selective degeneration of striatum in the brain. Octapeptide repeat expansion in the prion gene in Huntington disease like-1 has been also identified. Neuroacanthocytosis syndromes including McLeod syndrome and chorea-acanthocytosis cause acanthocytosis in the red blood cells and chorea due to the degeneration of caudate nucleus in the brain. The XK gene on the X chromosome is mutated to lose its function in McLeod syndrome. CHAC gene coding chorein is mutated to lead loss of function in chorea-acanthocytosis. Selective degeneration in the striatum, especially in the caudate nucleus might be associated with the molecular cascade of expanded polyglutamine or polyleucine or octapeptide and the loss of function of the XK protein and of chorein protein.
 ...
PMID:[Hereditary chorea--update]. 1565 35

A 45-year-old man developed chorea, behavioural changes, moderate amyotrophy and polyneuropathy. Hypertrophic cardiomyopathy and increased serum lactate dehydrogenase and creatine kinase (CK) were found. Acanthocytes were not detected. The absence of XK protein and faintly expressed Kell antigens on erythrocytes were found. Genetic test revealed a R133X mutation of the XK gene, confirming the McLeod syndrome. After 7 years he suddenly developed delirium followed by severe hypoglycaemia, hyperthermia, rhabdomyolysis, hepatic and renal failure. Malignant arrhythmia caused death.
 ...
PMID:The McLeod syndrome without acanthocytes. 1787 Jun 53