Phenotype-genotype correlations of pediatric patients with biallelic mutations in ABCA3 and SFTPB surfactant-related genes
Year: 2023
Type: conference-abstract
Abstract: Background : Among childhood interstitial lung diseases (chILD) etiologies, the main genetic causes are surfactant metabolism disorders. Mutations in the ATP-binding-cassette transporter A3 (ABCA3) and in SFTPB genes lead to ABCA3 and SP-B deficiencies. Both recessive diseases, they are the most severe causes of chILD. More than 200 different pathogenic mutations of ABCA3 were described since 2004. A classification of ABCA3 mutations according to their predicted functional effect was proposed in 2014. More than 40 recessive loss-of function mutations in SFTPB were identified. The main goal of this study is to describe the initial clinical presentation and evolution of patients with ABCA3 and SP-B deficiency in the French RespiRare cohort and to establish phenotype-genotype correlations that could guide management and genetic counseling. Methods : This is an observational, descriptive, retrospective, multicenter study. Data were collected between 2000 and 2023. Results : Among the 623 patients followed in the 41 RespiRare pediatric centers for ILD, 40 patients had bi-allelic mutations in ABCA3 and 12 patients carried bi-allelic mutations in SFTPB. Their phenotypic characteristics are being analyzed. Conclusion : Whereas the presentation and evolution of chILD due to ABCA3 mutations are variable, allowing to establish phenotype-genotype correlations, this is not the case for SFTPB mutations whose phenotype is always very severe.
Source: European Respiratory Journal
Authors: Manon Fleury, Alice Hadchouel, Julie Mazenq, Nouha Jedidi, Camille Fletcher, Myriam Benhamida, Pierrick Cros, Christophe Delacourt, Jean-Christophe Dubus, Carole Egron, Ralph Epaud, Michael Fayon, Aude Forgeron, Lisa Giovanni-Chami, Caroline Perisson, Hortense Petat, Marie-Catherine Renoux, Léa Roditis, Caroline Thumerelle, Clémentine Vigier, Aurore Couloumb, Laureline Berteloot, Chiara Sileo, Alix De Becdelièvre, Pascale Fanen, Marie Legendre, Camille Louvrier, Nadia Nathan
Institutions: Hôpital Armand-Trousseau, Assistance Publique – Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Aix-Marseille Université, Assistance Publique Hôpitaux de Marseille, Hôpital de la Timone, Hôpital Saint-Antoine, Centre Hospitalier Universitaire de Nantes, Hôpital Mère-Enfant, Centre Hospitalier Universitaire de Clermont-Ferrand, Hôpital Intercommunal de Créteil, Centre Hospitalier Universitaire de Bordeaux, Centre Hospitalier Universitaire de Nice, Hôpital Charles-Nicolle, Centre Hospitalier Universitaire de Toulouse, Centre Hospitalier Universitaire de Lille, Centre Hospitalier Universitaire de Rennes, Hôpitaux Universitaires Henri-Mondor
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4387980864