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

Fecha de publicación: 01/02/2022 Fecha Ahead of Print: 06/01/2022

Autores de IIS La Fe

Amparo Solé Jover

Autor

Participantes ajenos a IIS La Fe

Mondejar-Lopez, Pedro
Zolin, Anna
Garcia-Marcos, Patricia W.
Pastor-Vivero MD
Rosa-Silvestre, Maria
de Asis Sanchez-Martinez, Francisco
Salvatore, Donatello
Cimino, Giuseppe
Majo, Fabio
Asensio de la Cruz, Oscar
Calderazzo MA
Pizzamiglio, Giovanna
Castillo-Corullon, Silvia
Alvarez-Fernandez, Antonio
Gartner, Silvia
Padoan, Rita
Carnovale, Vincenzo
Salvatore, Marco
Moya-Quiles MR
Orenti, Annalisa
Glover, Guillermo
Sanchez-Solis, Manuel

Grupos

Infección Grave

Investigador Principal

María Ángeles Tormo Mas

Abstract

BACKGROUND: 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. METHODS: 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(1) (ppFEV(1)) was also analyzed using the 2010-2017 ECFSPR. RESULTS: 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(1) (90.8% vs. 78.6%), with 18.9% (most >40 years old) having a ppFEV(1)<70%. Additional ppFEV(1) decline (0.96% per year) was attributed to F508del/F508del genotype (p = 0.0007). None died or needed organ transplantation during the study period. CONCLUSIONS: 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(1) decline. However, some will develop progressive respiratory impairment during adulthood.

Datos de la publicación

ISSN/ISSNe:: 0954-6111, 1532-3064
Tipo:: Article
Páginas:: 106736-106736
DOI:: 10.1016/j.rmed.2022.106736
Factor de Impacto:: 1,112 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Filiaciones

Mondejar-Lopez, Pedro:: Pediatric Pulmonology and Cystic Fibrosis Unit, Hospital Clinico Universitario Virgen de la Arrixaca, Murcia, Spain

Department of Surgery, Paediatrics, Obstetrics and Genecology, Universidad de Murcia, Spain. Biomedical Research Institute of Murcia (IMIB), Murcia, Spain
Zolin, Anna:: Department of Clinical Sciences and Community Health, Laboratory of Medical Statistics, Epidemiology and Biometry G. A. Maccacaro, University of Milan, Milan, Italy
Garcia-Marcos, Patricia W.:: Pediatric Pulmonology and Cystic Fibrosis Unit, Hospital Clinico Universitario Virgen de la Arrixaca, Murcia, Spain
Pastor-Vivero MD:: Osakidetza. Organizacion Sanitaria Integrada Ezkerraldea-Enkarterri-Cruces, Hospital Universitario Cruces, Paediatrics, Cystic Fibrosis Unit, Bizkaia, Spain
Rosa-Silvestre, Maria:: Pediatric Pulmonology and Cystic Fibrosis Unit, Hospital Clinico Universitario Virgen de la Arrixaca, Murcia, Spain
de Asis Sanchez-Martinez, Francisco:: Pediatric Pulmonology and Cystic Fibrosis Unit, Hospital Clinico Universitario Virgen de la Arrixaca, Murcia, Spain
Salvatore, Donatello:: Cystic Fibrosis Centre, Hospital San Carlo, Potenza, Italy
Cimino, Giuseppe:: Lazio Reference Center for Cystic Fibrosis, Policlinico Umberto I University Hospital, Rome, Italy
Majo, Fabio:: Cystic Fibrosis Centre, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
Sole-Jover, Amparo:: Lung Transplantation and Cystic Fibrosis Unit, Hospital Universitario La Fe, Universidad de Valencia, Valencia, Spain
Asensio de la Cruz, Oscar:: Cystic Fibrosis Unit, Pediatric Pulmonology and Allergy Unit, Hospital Universitari Parc Tauli, Sabadell, Barcelona, Spain
Calderazzo MA:: Cystic Fibrosis Center, Hospital Giovanni Paolo II, Lamezia Terme, Italy
Pizzamiglio, Giovanna:: Cystic Fibrosis Center - Adult Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
Castillo-Corullon, Silvia:: Pediatric Pulmonology and Cystic Fibrosis Unit, Hospital Clínico Universitario, Valencia, Spain
Alvarez-Fernandez, Antonio:: Adult Cystic Fibrosis Unit, Pulmonology Service, Hospital Universitari Vall D'Hebron, Barcelona, Spain
Gartner, Silvia:: Pediatric Pulmonology and Cystic Fibrosis Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain
Padoan, Rita:: Department of Paediatrics, Cystic Fibrosis Regional Support Centre, University of Brescia, ASST Spedali Civili Brescia, Brescia, Italy
Carnovale, Vincenzo:: Department of Translational Medical Science, Cystic Fibrosis Centre, Adult Unit, University of Naples "Federico II", Italy
Salvatore, Marco:: Italian Cystic Fibrosis Registry, Rome, Italy, National Centre for Rare Diseases, Undiagnosed Rare Diseases Unit, Istituto Superiore di Sanità, Rome, Italy
Moya-Quiles MR:: Immunology Service, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain
Orenti, Annalisa:: Department of Clinical Sciences and Community Health, Laboratory of Medical Statistics, Epidemiology and Biometry G. A. Maccacaro, University of Milan, Milan, Italy
Glover, Guillermo:: Biochemistry and Clinical Genetic Centre. Hospital Clinico Universitario Virgen de la Arrixaca, Murcia, Spain
Sanchez-Solis, Manuel:: Pediatric Pulmonology and Cystic Fibrosis Unit, Hospital Clinico Universitario Virgen de la Arrixaca, Murcia, Spain

Department of Surgery, Paediatrics, Obstetrics and Genecology, Universidad de Murcia, Spain. Biomedical Research Institute of Murcia (IMIB), Murcia, Spain