Shwachman–Diamond syndrome due to biallelic <scp> <i>EFL1</i> </scp> variants with complex and fatal clinical course in early infancy
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.
Authors
- Miriam Erlacher (ORCID: https://orcid.org/0000-0002-7261-1447)
- Alan J. Warren (ORCID: https://orcid.org/0000-0001-9277-4553)
- Bernd Auber (ORCID: https://orcid.org/0000-0003-1880-291X)
- Patrick Revy (ORCID: https://orcid.org/0000-0003-0758-8022)
- Dirk Lebrecht (ORCID: https://orcid.org/0000-0002-4483-2920)
- Holger Cario (ORCID: https://orcid.org/0000-0002-6923-488X)
- Eva‐Maria Mair
- Sandra von Hardenberg (ORCID: https://orcid.org/0000-0002-3680-7450)
- Alexis Bertrand
- Shengjiang Tan
Institutions
- Inserm (FR)
- Université Paris Cité (FR)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- University of Cambridge (GB)
- Université Paris-Saclay (FR)
- University Medical Center Freiburg (DE)
- Medizinische Hochschule Hannover (DE)
- University Hospital Ulm (DE)
- Institut des Maladies Génétiques Imagine (FR)
- Medical Research Council (GB)
Publication Details
- Journal
- British Journal of Haematology
- Published
- 2024-10-08
- DOI
- https://doi.org/10.1111/bjh.19793
- Primary Topic
- Blood disorders and treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Shwachman Diamond Syndrome Foundation
- Cancer Research UK
- Rosetrees Trust
- Institut National de la Santé et de la Recherche Médicale
- Ligue Contre le Cancer
- Isaac Newton Trust
- Blood Cancer UK
- Medical Research Council