Rare CFTR large deletions: a series of cases / Grandes deleções raras no CFTR: uma série de casos

Aims: this paper aims to describe diagnosis and follow-up of patients affected by the Cystic Fibrosis (CF) manifestations and CFTR large deletions. For this, we performed a retrospective analysis of medical records, including genotyping and retrospective follow-up of clinical and lung function data. Electronic and printed medical records of patients followed at a referral outpatient clinic in CF were evaluated. Case description: we found that three patients had large deletions in the CFTRgene, being two of them heterozygous (heterozygous with deletion on exons from 2 to 3, and heterozygous for deletions on exons from 25 to 27) and one of them homozygous (homozygous for the deletions on exons from 19 to 21). One patient had a false negative result in complete genetic sequencing. All three received standard treatment for CF. Two patients died from CF pulmonary complications. Therefore, false negatives findings in CFTR sequencing for the diagnosis of CF are rare but may be more frequent in patients with large deletions. Conclusions: CFTR large deletions are associated with severe CF phenotypes

Objetivo: este trabalho tem como objetivo descrever o diagnóstico e o acompanhamento de pacientes acometidos pelas manifestações da fibrose cística e grandes deleções do gene CFTR. Para isso, realizamos análise retrospectiva de prontuários, incluindo genotipagem e acompanhamento retrospectivo de dados clínicos e de função pulmonar. Descrição dos casos: foram avaliados prontuários eletrônicos e impressos de pacientes acompanhados em ambulatório de referência em fibrose cística. Encontramos três pacientes com grandes deleções no gene CFTR, sendo dois deles heterozigotos (heterozigotos com deleção nos éxons de 2 a 3 e heterozigotos para deleções nos éxons de 25 a 27) e um deles homozigoto (homozigoto para as deleções nos éxons de 19 a 21,). Um paciente apresentou resultado falso negativo no sequenciamento genético completo. Todos os três receberam tratamento padrão para fibrose cística. Dois pacientes morreram de complicações pulmonares da fibrose cística. Portanto, achados falsos negativos no sequenciamento CFTR para o diagnóstico de fibrose cística são raros, mas podem ser mais frequentes em pacientes com grandes deleções. Conclusão: grandes deleções de CFTR estão associadas a fenótipos graves de FC

Translational Research in Cystic Fibrosis: From Bench to Beside.

Cystic fibrosis is the most common life-limiting recessive genetic disorder in Caucasian populations, characterized by the involvement of exocrine glands, causing multisystemic comorbidities. Since the first descriptions of pancreatic and pulmonary involvement in children, technological development and basic science research have allowed great advances in the diagnosis and treatment of cystic fibrosis. The great search for treatments that acted at the genetic level, despite not having found a cure for this disease, culminated in the creation of CFTR modulators, highly effective medications for certain groups of patients. However, there are still many obstacles behind the treatment of the disease to be discussed, given the wide variety of mutations and phenotypes involved and the difficulty of access that permeate these new therapies around the world.