Familial amyloid polyneuropathy: a proposal for an epidemiological study through the creation of a virtual platform
Polineuropatia amiloidótica familiar: uma proposta de estudo epidemiológico por meio da criação de uma plataforma virtual
Rev. bras. neurol; 57 (3), 2021
Publication year: 2021
Amyloidosis are characterized by mutations in the gene coding for transthyretin (TTR), located on chromosome 18. TTR is a set of four 127-aminoacid polypeptides structured as homotetrameric protein of 56 kDa with a secondary ß sheet structure. It plays the role of thyroxin (T4) carrier, and has a binding domain for retinol (vitamin A). It is synthesized in the liver, although a small quantity is also produced by the choroid plexus, and retinal cells. Mutations of this gene result in loss of tetramer stability. Insoluble amyloid fibrils (AF) are formed and deposited in tissues and organs. The abnormal aggregation of TTR protein trigger several syndromes, such as familial amyloid polyneuropathy (FAP-TTR), cardiomyopathies (CMP), and senile systemic amyloidosis (SSA). It is estimated there are 5,000 to 10,000 cases of FAP-TTR globally.
OBJECTIVE:
The study intends to develop an online platform for the diagnosis of FAP-TTR. The aim is to facilitate the diagnosis process and promote a tool for epidemiological study.METHODS:
The project was based on a literature review featuring clinical and epidemiological evidence for the development of a practical platform (applied research).RESULTS:
It was elaborated a platform containing a questionnaire to allow a more dynamic, cheaper, and efficient operation, mediated by a better characterization of the disease to enable its early diagnosis.CONCLUSION:
The platform might become a valuable resource for the characterization, diagnosis, and future epidemiological study of FAP-TTR
As amiloidoses se caracterizam por mutações no gene codificante da transtirretina (TTR) no cromossomo 18. A proteína TTR compõe-se de uma corrente de polipeptídios de 127 resíduos, que constituem uma proteína homotetramérica de 56kDa com estrutura secundária de folha ß, que serve como proteína de deslocamento para a tiroxina (T4), e uma proteína de ligação ao retinol (vitamina A). O principal local de produção dessa proteína é o fígado, embora uma pequena quantidade seja produzida pelo plexo coroide e pelas células retinianas. O gene codificante da TTR (18q11.2-12) é pequeno (7 kb) e contém quatro éxons. As mutações convertem-se em perda do equilíbrio do tetrâmero proteico. Surgem assim, fibrilas amiloides (FA) em cadeias não ramificadas de 10 a 12 nm de diâmetro e fibrilas indissolúveis, que se condensam nos tecidos e órgãos.