Vito Terlizzi1, Rita Padoan2, Laura Claut3, Carla Colombo3, Benedetta Fabrizzi4, Marco Lucarelli5,6, Sabina Maria Bruno5, Alice Castaldo7, Paolo Bonomi8, Giovanni Taccetti1, Antonella Tosco7. 1. Cystic Fibrosis Regional Reference Center, Department of Paediatric Medicine, Anna Meyer Children's University, 50139 Florence, Italy. 2. Cystic Fibrosis Regional Support Center, Department of Pediatrics, University of Brescia, ASST Spedali Civili Brescia, 25123 Brescia, Italy. 3. Cystic Fibrosis Regional Reference Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy. 4. Cystic Fibrosis Regional Reference Center, Mother-Child Department, United Hospitals, 60126 Ancona, Italy. 5. Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy. 6. Pasteur Institute Cenci Bolognetti Foundation, 00161 Rome, Italy. 7. Cystic Fibrosis Regional Reference Center, Paediatric Unit, Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy. 8. Freelance Statistician, 20122 Milan, Italy.
Abstract
BACKGROUND: There are no predictive factors of evolution of cystic fibrosis (CF) screen positive inconclusive diagnosis subjects (CFSPIDs). AIM: to define the role of the second CFTR variant as a predictive factor of disease evolution in CFSPIDs carrying the D1152H variant. METHODS: 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. RESULTS: 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 (p < 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. CONCLUSIONS: 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.
BACKGROUND: There are no predictive factors of evolution of cystic fibrosis (CF) screen positive inconclusive diagnosis subjects (CFSPIDs). AIM: to define the role of the second CFTR variant as a predictive factor of disease evolution in CFSPIDs carrying the D1152H variant. METHODS: 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. RESULTS: 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 (p < 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. CONCLUSIONS: 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.
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