Prevalence of germline GATA2 and SAMD9/9L variants in paediatric haematological disorders with monosomy 7.

Adolescent Child Child, Preschool Chromosome Deletion Chromosomes, Human, Pair 7 / genetics Female GATA2 Transcription Factor / genetics Germ-Line Mutation Hematologic Neoplasms / epidemiology High-Throughput Nucleotide Sequencing Humans Infant Infant, Newborn Intracellular Signaling Peptides and Proteins / genetics Male Myelodysplastic Syndromes / epidemiology Prevalence Tumor Suppressor Proteins / genetics

GATA2 SAMD9 SAMD9L monosomy 7 pediatrics

Journal

British journal of haematology

ISSN: 1365-2141

Titre abrégé: Br J Haematol

Pays: England

ID NLM: 0372544

Informations de publication

Date de publication:
12 2020

Historique:

received: 28 05 2020

accepted: 06 07 2020

pubmed: 10 8 2020

medline: 24 3 2021

entrez: 10 8 2020

Statut: ppublish

Résumé

Monosomy 7 (-7) occurs in various types of paediatric myeloid disorders and has a poor prognosis. Recent studies have demonstrated that patients with germline gain-of-function SAMD9/9L variants and loss-of-function GATA2 variants are prone to developing myelodysplastic syndrome (MDS) associated with -7. However, the prevalence of the genetic variants among paediatric haematologic disorders with -7 is unknown. The present study screened germline variants of GATA2 and SAMD9/9L in 25 patients with various types of paediatric haematological disorders associated with -7. The diagnoses of the 25 patients included MDS (n = 10), acute myeloid leukaemia (AML) and myeloid sarcomas (n = 9), juvenile myelomonocytic leukaemia (n = 3) and other disorders (n = 3). Seven patients with a germline pathogenic GATA2 variant were found. For SAMD9/9L screening, next-generation sequencing was used to detect low-abundance variants and found four novel germline variants. Functional analysis revealed that three out of the four variants showed growth-restricting capacity in vitro and thus, were judged to be pathogenic. Cases with GATA2 mutation tended to be older, compared to those with SAMD9/9L mutations. In conclusion, GATA2 and SAMD9/9L were sequenced in 25 patients with paediatric haematologic disorders associated with -7, and 40% of them were found to have some pathogenic germline variants in the three genes.

Identifiants

DOI: 10.1111/bjh.17006 PMID: 32770553

pubmed: 32770553

doi: 10.1111/bjh.17006

doi:

Substances chimiques

GATA2 Transcription Factor 0

GATA2 protein, human 0

Intracellular Signaling Peptides and Proteins 0

SAMD9 protein, human 0

SAMD9L protein, human 0

Tumor Suppressor Proteins 0

Types de publication

Clinical Trial Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

835-843

Subventions

Organisme : Japan Society for the Promotion of Science (JSPS)

ID : 17H04234

Organisme : Japan Society for the Promotion of Science (JSPS)

ID : 19H03627

Organisme : Japan Agency for Medical Research and development (AMED)

ID : 19ck0106467

Organisme : Takeda Science Foundation

Organisme : Grant-in-Aid for Scientific Research on Innovative Areas from MEXT

ID : 3905-A02

Organisme : National Center for Child Health and Development

ID : 2020A-1

Organisme : National Center for Child Health and Development

ID : 29-2

Informations de copyright

Références

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