A1006E is a Cystic Fibrosis (CF) mutation that is still not widely known. We report phenotypic features and geographic distribution of the largest cohort of people with CF (pwCF) carrying A1006E to date.
Study of European pwCF carrying A1006E mutation, included in the European CF Society Patient Registry (ECFSPR). Genotype, ancestries and all variables recorded were compared to a cohort of F508del/F508del patients. Rate of decline in percentage-of-predicted FEV (ppFEV) was also analyzed using the 2010-2017 ECFSPR.
44 pwCF carrying A1006E were reported (59% males), median age 33 years old (3-58), 54.5% Spanish and 40.9% Italian, most with ancestry in Murcia (Spain) and Lazio (Italy) regions. Compared to F508del homozygous, A1006E-pwCF were significantly older (75% vs. 52.5% ≥ 18 years old) and diagnosed at later median age (6.98 vs. 0.29 years); showed lower rates of meconium ileus (2.33% vs. 17.7%), pancreatic insufficiency (27.91% vs. 99.26%), diabetes (2.33% vs. 21.98%), liver disease (6.98% vs. 36.72%) and Pseudomonas aeruginosa chronic colonization (30.95% vs. 42.51%); and presented better nutrition (BMI z-score 0.44 vs. -0.43) and ppFEV (90.8% vs. 78.6%), with 18.9% (most >40 years old) having a ppFEV<70%. Additional ppFEV decline (0.96% per year) was attributed to F508del/F508del genotype (p = 0.0007). None died or needed organ transplantation during the study period.
A1006E-pwCF are mainly of Western Mediterranean Spanish and Italian descent. When compared with F508del/F508del-pwCF, they usually have a milder form of the disease, associated with pancreatic sufficiency and slower FEV decline. However, some will develop progressive respiratory impairment during adulthood.
Copyright © 2022 Elsevier Ltd. All rights reserved.
About The Expert
Pedro Mondejar-Lopez
Anna Zolin
Patricia W Garcia-Marcos
Mª Dolores Pastor-Vivero
Maria Rosa-Silvestre
Francisco de Asis Sanchez-Martinez
Donatello Salvatore
Giuseppe Cimino
Fabio Majo
Amparo Sole-Jover
Oscar Asensio de la Cruz
Maria Adelaide Calderazzo
Giovanna Pizzamiglio
Silvia Castillo-Corullon
Antonio Alvarez-Fernandez
Silvia Gartner
Rita Padoan
Vincenzo Carnovale
Marco Salvatore
Mª Rosa Moya-Quiles
Annalisa Orenti
Guillermo Glover
Manuel Sanchez-Solis
References
PubMed