[Paper-level Aggregated] PMCID: PMC3184204

Evidence Type(s): Predisposing, Diagnostic, Prognostic, Functional

Justification: Predisposing: The text indicates that the c.1061C>T and c.1063_1065delACA mutations in the GATA2 gene are associated with multigenerational transmission of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), suggesting a predisposition to these conditions. Diagnostic: The identification of GATA2 mutations as predisposing factors for MDS/AML can aid in the diagnosis of these conditions in affected families. Prognostic: The mention of these mutations being critical for effective prognosis indicates that they may provide information about the likely course or outcome of MDS/AML in affected individuals. Functional: The text discusses the differential effects of the mutations on transactivation of target genes, cellular differentiation, apoptosis, and global gene expression, indicating functional consequences of the variants.

Gene→Variant (gene-first): GATA2(2624):c.1061C>T GATA2(2624):c.1063_1065delACA GATA2(2624):p.Thr354Met SPI1(6688):p.Thr355del

Genes: GATA2(2624) SPI1(6688)

Variants: c.1061C>T c.1063_1065delACA p.Thr354Met p.Thr355del

[Paragraph-level] PMCID: PMC3184204 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predisposing, Diagnostic, Functional

Justification: Predisposing: The passage describes the discovery of the GATA2 gene as a predisposition gene for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), indicating that the variants are associated with inherited risk for developing these diseases. Diagnostic: The variants are used to define and classify familial forms of MDS and AML, as they are reported to segregate with the disease in multiple families, which supports their role in diagnosis. Functional: The passage mentions that the mutations have differential effects on transactivation of target genes, cellular differentiation, apoptosis, and global gene expression, indicating that they alter molecular or biochemical function.

Gene→Variant (gene-first): 2624:c.1061C>T 2624:c.1063_1065delACA 2624:p.Thr354Met 6688:p.Thr355del

Genes: 2624 6688

Variants: c.1061C>T c.1063_1065delACA p.Thr354Met p.Thr355del

[Paragraph-level] PMCID: PMC3184204 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predisposing, Diagnostic, Functional

Justification: Predisposing: The passage describes the discovery of the GATA2 gene as a predisposition gene for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), indicating that the variants are associated with inherited risk for developing these diseases. Diagnostic: The variants are used to define and classify familial forms of MDS and AML, as they are reported to segregate with the disease in multiple families, which supports their role in diagnosis. Functional: The passage mentions that the mutations have differential effects on transactivation of target genes, cellular differentiation, apoptosis, and global gene expression, indicating that they alter molecular or biochemical function.

Gene→Variant (gene-first): 2624:c.1061C>T 2624:c.1063_1065delACA 2624:p.Thr354Met 6688:p.Thr355del

Genes: 2624 6688

Variants: c.1061C>T c.1063_1065delACA p.Thr354Met p.Thr355del