Supplementary Material for: A unique combination of heterozygous CFTR gene variants in a person with cystic fibrosis and M. abscessus infection

Introduction: Cystic fibrosis (CF) is a genetic disorder caused by mutations in the CFTR gene. A minority of people with CF carry two heterozygous CFTR mutations other than the common Phe508del, complicating diagnosis and treatment. Case presentation: We report the case of a 25-year-old South American male diagnosed with CF respiratory disease, characterized by a history of recurrent infections, pulmonary Mycobacterium abscessus infection, airway disease on high-resolution CT, and an elevated sweat chloride level (74 mmol/L). Exome sequencing identified a unique combination of CFTR mutations: a pathogenic frameshift variant (c.2052dup) and a variant of unknown clinical significance (c.710A>C). Notably, there were no signs of pancreatic insufficiency. Rectal mucosal organoid cultures demonstrated residual CFTR function with responsiveness to ivacaftor and the combination of elexacaftor, tezacaftor, and ivacaftor. Conclusion: This case highlights a unique combination of heterozygous CFTR variants in a person with late-onset CF respiratory disease, which may be amenable to CFTR modulation therapy.Introduction: 囊性纤维化（Cystic fibrosis, CF）是一类由CFTR基因突变导致的遗传性疾病。仅少数CF患者携带有别于常见Phe508del突变的双杂合CFTR突变，这给临床诊断与治疗带来了挑战。Case presentation: 本文报告1例25岁南美男性囊性纤维化呼吸道疾病病例。该患者存在反复感染病史、肺部脓肿分枝杆菌（Mycobacterium abscessus）感染、高分辨率CT显示气道病变，且汗液氯离子水平升高（74 mmol/L）。外显子组测序（Exome sequencing）检出一组独特的CFTR突变组合：1种致病性移码变异（c.2052dup）与1种临床意义未明变异（c.710A>C）。值得关注的是，该患者未出现胰腺功能不全征象。直肠黏膜类器官培养实验证实其存在残余CFTR功能，且对伊伐卡托（ivacaftor）以及依伐卡托（elexacaftor）、替扎卡托（tezacaftor）与伊伐卡托联合用药方案具有应答反应。Conclusion: 本病例揭示了1例迟发性囊性纤维化呼吸道疾病患者所携带的独特杂合CFTR变异组合，该类患者或可受益于CFTR靶向调节治疗。