Novel frameshift variant of the CFTR gene: S511Lfs*2 from phenotype to molecular predictions
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Novel frameshift variant of the CFTR gene: S511Lfs*2 from phenotype to molecular predictions Thaiane Rispoli1,2 · Grazielle Motta Rodrigues2,3 · Mayara Jorgens Prado1,2 · Leonardo Araújo Pinto4 · Marcelo Tadday Rodrigues5 · Cynthia Rocha Dullius5 · Tarciana Grandi2 · Cláudia Maria Dornelles da Silva2 · José Eduardo Vargas6 · Maurício Menegatti Rigo7 · Maria Lucia Rossetti1,8 Received: 27 March 2020 / Revised: 9 July 2020 / Accepted: 19 July 2020 © Springer Nature B.V. 2020
Abstract Cystic fibrosis (CF) is a genetic disease caused by variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. There are over 2,000 different pathogenic and non-pathogenic variants described in association with a broad clinical heterogeneity. In this work, we identified a novel variant S511Lfs*2 in CFTR gene that has not been reported in patients with CF. The patient was a female genotyped with c.1000C>T (legacy name: R334W) variant (pathogenic, CF-causing) and the novel variant (S511Lfs*2). We verified the amino acid sequence, the protein structure, and predicted the pathogenicity employing computational analysis. Our findings showed that S511Lfs*2 is a frameshift variant and suggest that it is associated with severe CF phenotype, as it leads to a lack of CFTR protein synthesis, and consequently the loss of its functional activity. Keywords Cystic fibrosis · S511Lfs*2 variant · CFTR gene · CFTR protein · Frameshift variant
Introduction * Thaiane Rispoli [email protected] 1
Programa de Pós‑Graduação em Biologia Celular e Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
2
Centro de Desenvolvimento Científico e Tecnológico, Secretaria da Saúde do Estado do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
3
Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
4
Hospital São Lucas da PUCRS, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
5
Serviço de Fibrose Cística ‑ Adultos, Serviço de Pneumologia, Hospital São Lucas da PUCRS, Porto Alegre, Rio Grande do Sul, Brazil
6
Instituto de Ciências Biológicas, Universidade de Passo Fundo, Passo Fundo, Rio Grande do Sul, Brazil
7
Programa de Pós-Graduação em Pediatria e Saúde da Criança, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
8
Programa de Pós‑Graduação em Biologia Celular e Molecular Aplicada à Saúde, Universidade Luterana do Brazil, Canoas, Rio Grande do Sul, Brazil
Cystic fibrosis (CF-OMIM 219700) is an autosomal recessive inherited disorder caused by variants in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene [1]. The CFTR gene encodes a protein of 1480 residues in length (UniProt ID: P13569). This protein belongs to the ATP-binding cassette (ABC) transporter superfamily and its function is related to the transport of chloride ions across cell membranes [2, 3], regulation of airway
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