Study Of A Family With A Thr69Ala Mutation Of TTR Gene In Familial Amyloid Polyneuropathy Disease

[Background and Objective]Familial amyloid polyneuropathy (FAP) is an autosomal dominant disease, is no difference in sex ratio。BUT can be occasionally inincidence in one generation because explicit failure. Characterizing by amyloid deposition in different organs.. It is characterized by polyneuropathy, autonomic neuropathy, vitreous opacities, heart disease, renal failure and multiple organs failure. In 1952, Andrade was first reported in Portugal. Since the disease was confirmed in many race of the world, especially in northern Sweden, Japan, and Majorca.Although FAP have a detailed description of pedigree and epidemiological statistics in many foreign countriesand have their race gene "mutation hot spots" todescribe. Among them, the TTR gene mutation of 30 amino acid is substituted bymethionine (Met30) is best known。THE mutations in almost Portuguese families is MET30。In Taiwan, Only a few families have confirmed this disease。It was reported that Taiwan's hot spot mutation is the 97 amino acids mutated to serine (Ala97Ser)。In China, only a few families were reported due to the economic and medical reasons. Hot mutations, common clinical phenotype and genotype of FAP in China ware still not clear. In this study, we collected detailed and completed clinical data of 67 patients of five generations for the first time in China and conducted pathology, physiology and genetic studies. And we hope to discovery a new genes or new mutations in position.and provide information to our domestic "hot spot mutation" of FAP.[Objective]Ten familial amyloidosis polyneuropathy (FAP) patients with TTR (Transthyretin) Thr69Ala mutation in five generations from Anhui Province, China were reported. [Method] Detailed physical examinations were performed on 32 family members in five generations in the family, including the proband. Two patients and two family members underwent electromyogram and nerve conduction velocity test. The proband and her sister underwent sural nerve biopsy. Blood samples from 32 members were collected for gene mutation test. [Results] Six survived patients in the family had Thr69Ala mutation of TTR gene and eight asymptomatic TTRThr69Ala mutation carriers were also found. No above change were not found in 18 cases of asymptomatic family members and 200 normal controls. All patients presented with varying degrees of autonomic nerve dysfunction and peripheral sensory dysfunction and mild to moderate muscle atrophy and weakness. Four patients had disc herniation. In 2 patients underwent nerve biopsy, Amyloid-P and Congo red positive amyloid plaque deposits were confirmed under light microscope and the electron microscope showed increased collagen fibers in endoneurium, degenerated Schwann cells, separated and disintegrated myelin lamellar, concentric circles structure, disappeared axon. [Conclusion] The family is the first familial amyloid polyneuropathy family with complete clinical data in China, including 67 patients from 5 generations and we found a new mutation (Thr69Ala) of TTR gene in FAP, which may affect the special clinical symptom--disc herniation.