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

Autor: Mondejar-Lopez P; 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. Electronic address: mondejarp@um.es., Zolin A; Department of Clinical Sciences and Community Health, Laboratory of Medical Statistics, Epidemiology and Biometry G. A. Maccacaro, University of Milan, Milan, Italy., Garcia-Marcos PW; 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 M; Pediatric Pulmonology and Cystic Fibrosis Unit, Hospital Clinico Universitario Virgen de la Arrixaca, Murcia, Spain., de Asis Sanchez-Martinez F; Pediatric Pulmonology and Cystic Fibrosis Unit, Hospital Clinico Universitario Virgen de la Arrixaca, Murcia, Spain., Salvatore D; Cystic Fibrosis Centre, Hospital San Carlo, Potenza, Italy., Cimino G; Lazio Reference Center for Cystic Fibrosis, Policlinico Umberto I University Hospital, Rome, Italy., Majo F; Cystic Fibrosis Centre, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Sole-Jover A; Lung Transplantation and Cystic Fibrosis Unit, Hospital Universitario La Fe, Universidad de Valencia, Valencia, Spain., Asensio de la Cruz O; 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 G; Cystic Fibrosis Center - Adult Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy., Castillo-Corullon S; Pediatric Pulmonology and Cystic Fibrosis Unit, Hospital Clínico Universitario, Valencia, Spain., Alvarez-Fernandez A; Adult Cystic Fibrosis Unit, Pulmonology Service, Hospital Universitari Vall D'Hebron, Barcelona, Spain., Gartner S; Pediatric Pulmonology and Cystic Fibrosis Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain., Padoan R; Department of Paediatrics, Cystic Fibrosis Regional Support Centre, University of Brescia, ASST Spedali Civili Brescia, Brescia, Italy., Carnovale V; Department of Translational Medical Science, Cystic Fibrosis Centre, Adult Unit, University of Naples 'Federico II', Italy., Salvatore M; 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 A; Department of Clinical Sciences and Community Health, Laboratory of Medical Statistics, Epidemiology and Biometry G. A. Maccacaro, University of Milan, Milan, Italy., Glover G; Biochemistry and Clinical Genetic Centre. Hospital Clinico Universitario Virgen de la Arrixaca, Murcia, Spain., Sanchez-Solis M; 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.
Jazyk: angličtina
Zdroj: Respiratory medicine [Respir Med] 2022 Feb; Vol. 192, pp. 106736. Date of Electronic Publication: 2022 Jan 06.
DOI: 10.1016/j.rmed.2022.106736
Abstrakt: 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.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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