Shwachman-Diamond syndrome due to biallelic EFL1 variants with complex and fatal clinical course in early infancy.

Autor: Cario H; Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.; Center for Rare Hematopoietic Disorders and Immunodeficiencies (ZSHI), Rare Disease Center, University Medical Center Ulm, Ulm, Germany., Bertrand A; Laboratory of Genome Dynamics in the Immune System, INSERM UMR 1163, Imagine Institute, Paris, France.; Université Paris Cité, Imagine Institute, Paris, France.; Université Paris-Saclay, Paris, France., Tan S; Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.; Wellcome Trust-Medical Research Council Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus, Cambridge, UK.; Department of Haematology, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge School of Clinical Medicine, Cambridge, UK., Auber B; Department of Human Genetics, Hannover Medical School, Hannover, Germany., Erlacher M; Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.; Center for Pediatrics and Adolescent Medicine, Pediatric Hematology and Oncology, University Medical Center Freiburg, Freiburg, Germany., Mair EM; Division of Neonatology and Pediatric Intensive Care Medicine, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany., von Hardenberg S; Department of Human Genetics, Hannover Medical School, Hannover, Germany., Lebrecht D; Center for Pediatrics and Adolescent Medicine, Pediatric Hematology and Oncology, University Medical Center Freiburg, Freiburg, Germany., Revy P; Laboratory of Genome Dynamics in the Immune System, INSERM UMR 1163, Imagine Institute, Paris, France.; Université Paris Cité, Imagine Institute, Paris, France., Warren AJ; Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.; Wellcome Trust-Medical Research Council Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus, Cambridge, UK.; Department of Haematology, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2024 Dec; Vol. 205 (6), pp. 2363-2369. Date of Electronic Publication: 2024 Oct 08.
DOI: 10.1111/bjh.19793
Abstrakt: Shwachman-Diamond syndrome represents a clinically and genetically heterogeneous disorder. We report on an infant with a very severe, fatal clinical course caused by biallelic EFL1 variants: c.89A>G, p.(His30Arg), and c.2599A>G, p.(Asn867Asp). Functional analysis of patient-derived B-lymphoblastoid and SV40-transformed fibroblast cell lines suggests that the compound heterozygous EFL1 variants impaired mature ribosome formation leading to compromised protein synthesis, ultimately resulting in a severe form of Shwachman-Diamond syndrome.
(© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: