Terlizzi Vito, Padoan Rita, Claut Laura, Colombo Carla, Fabrizzi Benedetta, Lucarelli Marco, Bruno Sabina Maria, Castaldo Alice, Bonomi Paolo, Taccetti Giovanni, Tosco Antonella
Cystic Fibrosis Regional Reference Center, Department of Paediatric Medicine, Anna Meyer Children's University, 50139 Florence, Italy.
Cystic Fibrosis Regional Support Center, Department of Pediatrics, University of Brescia, ASST Spedali Civili Brescia, 25123 Brescia, Italy.
Diagnostics (Basel). 2020 Dec 12;10(12):1080. doi: 10.3390/diagnostics10121080.
There are no predictive factors of evolution of cystic fibrosis (CF) screen positive inconclusive diagnosis subjects (CFSPIDs).
to define the role of the second variant as a predictive factor of disease evolution in CFSPIDs carrying the D1152H variant.
We retrospectively evaluated clinical characteristics and outcome of CFSPIDs carrying the D1152H variant followed at five Italian CF centers. CFSPIDs were divided in two groups: Group A: compound heterozygous for D1152H and a CF-causing variant; Group B: compound heterozygous for D1152H and a: (i) non CF-causing variant, (ii) variant with varying clinical consequences, or (iii) variant with unknown significance. The variants were classified according to CFTR2 mutation database.
We enrolled 43 CFSPIDs with at least one D1152H variant: 28 (65.1%) were classified in the group A, and 15 (34.9%) in the Group B. CFSPIDs of group A had the first IRT significantly higher compared to those of group B ( < 0.05) and had a more severe clinical outcome during the follow-up. At the end of the study period, after a mean follow-up of 40.6 months (range 6-91.6), 4 (9.3%) out of 43 CFSPIDs progressed to CFTR-RD or CF. All these subjects were in the group A.
The genetic profile could help predict the risk of disease evolution in CFSPIDs carrying D1152H, revealing the subjects that need a more frequent follow-up.
目前尚无针对囊性纤维化（CF）筛查呈阳性但诊断不确定的受试者（CFSPIDs）病情进展的预测因素。
确定第二个变异体在携带D1152H变异体的CFSPIDs疾病进展预测因素中的作用。
我们回顾性评估了在五个意大利CF中心随访的携带D1152H变异体的CFSPIDs的临床特征和结局。CFSPIDs被分为两组：A组：D1152H与一个导致CF的变异体的复合杂合子；B组：D1152H与以下变异体的复合杂合子：（i）非致CF变异体，（ii）具有不同临床后果的变异体，或（iii）意义不明的变异体。这些变异体根据CFTR2突变数据库进行分类。
我们纳入了43例至少携带一个D1152H变异体的CFSPIDs：28例（65.1%）被分类为A组，15例（34.9%）被分类为B组。A组CFSPIDs的首次IRT显著高于B组（<0.05），且在随访期间临床结局更严重。在研究期结束时，平均随访40.6个月（范围6 - 91.6个月）后，43例CFSPIDs中有4例（9.3%）进展为CFTR-RD或CF。所有这些受试者均在A组中。
基因谱有助于预测携带D1152H的CFSPIDs疾病进展的风险，识别出需要更频繁随访的受试者。
