Prevalence of germline GATA2 and SAMD9/9L variants in paediatric haematological disorders with monosomy 7.
Br J Haematol
; 191(5): 835-843, 2020 12.
Article
in En
| MEDLINE
| ID: mdl-32770553
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Myelodysplastic Syndromes
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Germ-Line Mutation
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Hematologic Neoplasms
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Tumor Suppressor Proteins
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Intracellular Signaling Peptides and Proteins
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GATA2 Transcription Factor
Type of study:
Clinical_trials
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Limits:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
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Newborn
Language:
En
Journal:
Br J Haematol
Year:
2020
Document type:
Article
Affiliation country: