Geographic distribution and phenotype of European people with cystic fibrosis carrying A1006E mutation

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 Reg...

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Published in:Respiratory medicine Vol. 192; p. 106736
Main Authors: Mondejar-Lopez, Pedro, Zolin, Anna, Garcia-Marcos, Patricia W, Pastor-Vivero, Mª Dolores, Rosa-Silvestre, Maria, de Asis Sanchez-Martinez, Francisco, Salvatore, Donatello, Cimino, Giuseppe, Majo, Fabio, Sole-Jover, Amparo, Asensio de la Cruz, Oscar, Calderazzo, Maria Adelaide, Pizzamiglio, Giovanna, Castillo-Corullon, Silvia, Alvarez-Fernandez, Antonio, Gartner, Silvia, Padoan, Rita, Carnovale, Vincenzo, Salvatore, Marco, Moya-Quiles, Mª Rosa, Orenti, Annalisa, Glover, Guillermo, Sanchez-Solis, Manuel
Format: Journal Article
Language:English
Published: England 01.02.2022
Subjects:
Adult
Cystic Fibrosis - diagnosis
Cystic Fibrosis - epidemiology
Cystic Fibrosis - genetics
Cystic Fibrosis Transmembrane Conductance Regulator - genetics
Female
Homozygote
Humans
Male
Mutation - genetics
Phenotype
Cystic fibrosis
Genotype
Phenotype
Missense mutation
A1006E
ISSN:1532-3064, 1532-3064
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Summary: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.
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ISSN:1532-3064
1532-3064
DOI:10.1016/j.rmed.2022.106736