文摘
Familial amyloidotic polyneuropathy represents an autosomal dominant disorder due to missense mutations in the transthyretin (TTR) gene (MIM *176300). Transthyretin gene is a small gene (7.6 kb) synthesised mainly in the liver and in the choroid plexus. A single promoter has been identified, located at −25 upstream the ATG initiation codon. The clinical picture of the disease is characterised by a mixed peripheral neuropathy associated with autonomic disturbances. Restrictive cardiomyopathy and vitreous opacities are additional signs. It has been established that amyloid deposition is the main event causing peripheral neuropathy, but its amount does not correlate with the phenotype. Moreover, some authors reported a primary involvement of the dorsal root ganglia, suggesting that the CSF TTR might play a role in FAP pathogenesis. We performed transcriptional analysis by RT-PCR on human foetal tissues (liver, spinal cord, cerebellum, brain, kidney, eyes, heart, and skeletal muscle) as well as on human adult liver, brain, cerebellum and choroid plexus (surgical specimens) and from livers obtained from FAP transplanted patients. We discovered and characterised a novel upstream promoter (−109), very active in the cerebellum, as well in the liver, and coexisting with the downstream one in both tissues. The two promoters are active in both foetal and adult tissues as well in the patients' livers. We also demonstrated that TTR is expressed at very high level in spinal cord and cerebellum, suggesting that this protein might play a role in the central nervous system and particularly in the cerebral and spinal fluids.
