However, in 2002, the experimentally observed mutation of the gene leading to the BHC phenotype was identified, solidifying benign hereditary chorea as a disorder. In 1967, several families were examined and discovered to have movements that were abnormal and random since childhood. These random movements were not violent movements, and gave the person a "general appearance of restlessness." The movements occurred mostly in the hands and arms, and some also experienced them in their tongues, facial muscles, and lower body. Movements in the lower extremities, if severe enough, could cause changes in gait. The families were given a Wechsler Intelligence Scale test, scoring average relative to others in their community. Aside from the aforementioned symptoms, the peoples physical and neurological characteristics were normal. The observed symptoms were put in the category of chorea. Researchers made pedigrees of the families they studied and determined that BHC was an autosomal dominant disorder. By studying a Dutch family, the disorder was discovered to be linked to chromosome 14. In 2002, an Italian family was studied, and they had the same linkage to chromosome 14 as the Dutch family did. Looking closer at the region of the chromosome suspected of causing the disorder, researchers discovered that there was a 1.2 Mb deletion in the DNA that resulted in the loss of the TITF-1 gene. This meant that mutations in the TITF-1 gene were likely the reason behind the symptoms of BHC.
There was no rebound effect following withdrawal of treatment, but a gradual return to pre-treatment bowel movement frequency should be expected. Minimal distribution of the drug occurs beyond the immediate gastrointestinal tissues. Lubiprostone is rapidly metabolized by reduction/oxidation, mediated by carbonyl reductase. There is no metabolic involvement of the hepatic cytochrome P450 system. The measurable metabolite, M3, exists in very low levels in plasma and makes up less than 10% of the total administered dose. Data indicate that metabolism occurs locally in the stomach and jejunum. References
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