ArticleThe Journal of clinical investigation2017
Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond-like features.
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Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.
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88citing papers in PubMed, 1 pooled it
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Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 171 citations in OpenAlex.
- A Case Report of Shwachman-Diamond Syndrome Caused by Heterozygous Variants in the EFL1 Gene and Literature Review.Molecular genetics & genomic medicine · 2026Pooled it
- GTPase cycle and ER membrane regulate cargo handover during cotranslational protein targeting.Science advances · 2026Article
- Human SRP Subunits Coordinate Protein Targeting and mRNA Quality Control.bioRxiv : the preprint server for biology · 2026Article
- Genetic influences on haematopoiesis.Nature reviews. Genetics · 2026Review
- Homozygous Pathogenic Variant in Elongation Factor-Like 1 (EFL1) as a Causal Factor in Shwachman-Diamond Syndrome 2 in a Palestinian Child, With Distinct Ocular Manifestations.Molecular genetics & genomic medicine · 2026Article
- From ribosomopathies to therapeutic targets: ribosomal alterations in pediatric leukemogenesis and tumorigenesis.Frontiers in oncology · 2026Review
- A De Novo Splicing Mutation of SRP72 in Bone Marrow Failure Syndrome Type 1: Case Report and Review of the Literature.Molecular genetics & genomic medicine · 2026Review
- Temporal Regulation of Signal Recognition Particle During Translation.Journal of molecular biology · 2025Article
- A nitrogen-containing diphyllin derivative C156-P1 exhibited broad-spectrum antiviral activity againstAntimicrobial agents and chemotherapy · 2025Article
- Review
- ATP13A1 engages SEC61 to facilitate substrate-specific translocation.Science advances · 2025Article
- Inherited Predispositions to Myeloid Neoplasms: Pathogenesis and Clinical Implications.Annual review of pathology · 2025Review
- Case Report: A case report and literature review of shwachman-diamond syndrome concurrent with klinefelter syndrome.Frontiers in pediatrics · 2025Article
- Clinical characteristics and genetic mutation analysis in 18 pediatric patients with Shwachman-Diamond syndrome.Frontiers in genetics · 2025Article
- Shwachman-Diamond syndrome due to biallelic EFL1 variants with complex and fatal clinical course in early infancy.British journal of haematology · 2024Article
- A JAGN1-associated severe congenital neutropenia zebrafish model revealed an altered G-CSFR signaling and UPR activation.Blood advances · 2024Article
- Lethal Complications and Complex Genotypes in Shwachman Diamond Syndrome: Report of a Family with Recurrent Neonatal Deaths and a Case-Based Brief Review of the Literature.Children (Basel, Switzerland) · 2024Review
- The metabolic basis of inherited neutropenias.British journal of haematology · 2024Review
- Shwachman-Diamond syndromes: clinical, genetic, and biochemical insights from the rare variants.Haematologica · 2023Article
- Spectrum of diabetes mellitus in patients with Shwachman-Diamond syndrome: case report and review of the literature.Italian journal of pediatrics · 2023Review
28 more citing papers are in PubMed but not listed here.
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Authors and funding
50 authors at 13 institutions in 4 countries.
Raphael CarapitoLaboratoire d'ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, INSERM UMR - S1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
Martina KonantzDepartment of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Catherine PaillardLaboratoire d'ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, INSERM UMR - S1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
Zhichao MiaoArchitecture et Réactivité de l'ARN, CNRS UPR 9002, LabEx NetRNA, Institut de Biologie Moléculaire et Cellulaire, Université de Strasbourg, Strasbourg, France.
Angélique PichotLaboratoire d'ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, INSERM UMR - S1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
Magalie S LeducDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Yaping YangDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Katie L BergstromDepartment of Pediatrics, Hematology-Oncology Section, Texas Children's Hematology and Cancer Centers, Baylor College of Medicine, Houston, Texas, USA.
Donald H MahoneyDepartment of Pediatrics, Hematology-Oncology Section, Texas Children's Hematology and Cancer Centers, Baylor College of Medicine, Houston, Texas, USA.
Deborah L ShardyDepartment of Pediatrics, Hematology-Oncology Section, Texas Children's Hematology and Cancer Centers, Baylor College of Medicine, Houston, Texas, USA.
Ghada AlsalehLaboratoire d'ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, INSERM UMR - S1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
Lydie NaegelyLaboratoire d'ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, INSERM UMR - S1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
Aline KolmerLaboratoire d'ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, INSERM UMR - S1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
Nicodème PaulLaboratoire d'ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, INSERM UMR - S1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
Antoine HanauerLaboratoire d'ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, INSERM UMR - S1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
Véronique RolliLaboratoire d'ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, INSERM UMR - S1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
Joëlle S MüllerDepartment of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Elisa AlghisiDepartment of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Loïc SauteurDepartment of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Cécile MacquinLaboratoire d'ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, INSERM UMR - S1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
Aurore MorlonBIOMICA SAS, Strasbourg, France.
Consuelo Sebastia SanchoService de Radiologie Pédiatrique, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
Patrizia Amati-BonneauCNRS UMR 6015, INSERM UMR - S1083, MitoVasc Institute, Angers University, Angers, France.
Vincent ProcaccioCNRS UMR 6015, INSERM UMR - S1083, MitoVasc Institute, Angers University, Angers, France.
Anne-Laure Mosca-BoidronLaboratoire de Cytogénétique, Pôle de Biologie, Centre Hospitalier Universitaire (CHU) de Dijon, Dijon, France.
Nathalie MarleLaboratoire de Cytogénétique, Pôle de Biologie, Centre Hospitalier Universitaire (CHU) de Dijon, Dijon, France.
Naël OsmaniLaboratoire d'ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, INSERM UMR - S1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
Olivier LefebvreLaboratoire d'ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, INSERM UMR - S1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
Jacky G GoetzLaboratoire d'ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, INSERM UMR - S1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
Sule UnalDivision of Pediatric Hematology, Hacettepe University Medical Faculty, Sihhiye, Ankara, Turkey.
Nurten A AkarsuGene Mapping Laboratory, Department of Medical Genetics, Hacettepe University Medical Faculty, Sihhiye, Ankara, Turkey.
Mirjana RadosavljevicLaboratoire d'ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, INSERM UMR - S1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
Marie-Pierre ChenardDépartement de Pathologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
Fanny RiallandService d'Oncologie et Hématologie Pédiatrique, Hôpital Femmes-enfants-adolescents, CHU de Nantes, Nantes, France.
Audrey GrainService d'Oncologie et Hématologie Pédiatrique, Hôpital Femmes-enfants-adolescents, CHU de Nantes, Nantes, France.
Marie-Christine BénéService d'Hématologie Biologique, CHU de Nantes, Nantes, France.
Marion EveillardService d'Hématologie Biologique, CHU de Nantes, Nantes, France.
Marie VincentService de Génétique Médicale, Hôpital Femmes-enfants-adolescents, CHU de Nantes, Nantes, France.
Julien GuyService d'Hématologie Biologique, Pôle Biologie, CHU de Dijon, Dijon, France.
Laurence FaivreService de Génétique, Hôpital d'enfants, CHU de Dijon, Dijon, France.
Christel Thauvin-RobinetService de Génétique, Hôpital d'enfants, CHU de Dijon, Dijon, France.
Julien ThevenonService de Génétique, Hôpital d'enfants, CHU de Dijon, Dijon, France.
Kasiani MyersDivision of Blood and Marrow Transplantation and Immune Deficiency, The Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Mark D FlemingDepartment of Pathology, Boston Children's Hospital, and.
Akiko ShimamuraDana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA.
Elodie Bottollier-LemallazService d'Hématologie et Oncologie Pédiatrique, Hôpital d'enfants, CHU de Dijon, Dijon, France.
Eric WesthofArchitecture et Réactivité de l'ARN, CNRS UPR 9002, LabEx NetRNA, Institut de Biologie Moléculaire et Cellulaire, Université de Strasbourg, Strasbourg, France.
Claudia LengerkeDepartment of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Bertrand IsidorService de Génétique Médicale, Hôpital Femmes-enfants-adolescents, CHU de Nantes, Nantes, France.
Seiamak BahramLaboratoire d'ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, INSERM UMR - S1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
Inserm · FRHôpital d'Enfants · FRUniversity of Basel · CHCentre National de la Recherche Scientifique · FRChildren's Cancer Center · USCHU Dijon Bourgogne · FRBaylor College of Medicine · USCentre Hospitalier Universitaire de Nantes · FRHacettepe University · TRHôpitaux Universitaires de Strasbourg · FRBoston Children's Hospital · USCincinnati Children's Hospital Medical Center · USHarvard University · US
Funding
Translational Studies of Inherited Marrow Failure and Myelodysplastic SyndromesR24DK099808 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ABKOWITZ, JANIS L, EBERT, BENJAMIN LEVINE · 2013 to 2017
$8.2MNIDDK NIH HHS R24 DK099808
Abstract
Shwachman-Diamond syndrome (SDS) (OMIM #260400) is a rare inherited bone marrow failure syndrome (IBMFS) that is primarily characterized by neutropenia and exocrine pancreatic insufficiency. Seventy-five to ninety percent of patients have compound heterozygous loss-of-function mutations in the Shwachman-Bodian-Diamond syndrome (sbds) gene. Using trio whole-exome sequencing (WES) in an sbds-negative SDS family and candidate gene sequencing in additional SBDS-negative SDS cases or molecularly undiagnosed IBMFS cases, we identified 3 independent patients, each of whom carried a de novo missense variant in srp54 (encoding signal recognition particle 54 kDa). These 3 patients shared congenital neutropenia linked with various other SDS phenotypes. 3D protein modeling revealed that the 3 variants affect highly conserved amino acids within the GTPase domain of the protein that are critical for GTP and receptor binding. Indeed, we observed that the GTPase activity of the mutated proteins was impaired. The level of SRP54 mRNA in the bone marrow was 3.6-fold lower in patients with SRP54-mutations than in healthy controls. Profound reductions in neutrophil counts and chemotaxis as well as a diminished exocrine pancreas size in a SRP54-knockdown zebrafish model faithfully recapitulated the human phenotype. In conclusion, autosomal dominant mutations in SRP54, a key member of the cotranslation protein-targeting pathway, lead to syndromic neutropenia with a Shwachman-Diamond-like phenotype.
Indexed as
AnimalsBone Marrow DiseasesChildCongenital Bone Marrow Failure SyndromesDNA Mutational AnalysisExocrine Pancreatic InsufficiencyFemaleGenetic Association StudiesHumansInfantLipomatosisMaleModels, MolecularNeutropeniaPancreas, ExocrinePhenotypeSignal Recognition ParticleSRP54 protein, human
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