What question did this study set out to answer?

This research seeks to clarify the relationship between GATA2 mutations and clinical features in affected individuals.

January 17, 2026Open Access

GATA2 at 14: genotype-phenotype correlations

Key Points

This research seeks to clarify the relationship between GATA2 mutations and clinical features in affected individuals.
Reviewed hospital records and referrals of 232 individuals with GATA2 mutations.
Categorized mutations based on their effects on GATA2 protein functionality.
Used regression models to assess the relationship between mutation groups and symptom onset.
Identified distinct hazard ratios for different mutation types, indicating variable onset age.
Truncation and Null mutations associated with earlier onset of symptoms and higher risk.
Specific ZF2 mutations correlated with significantly earlier disease presentation.

Abstract

GATA2 mutations cause adult-onset bone-marrow failure characterized by cytopenias, infections and increased risk of myeloid malignancy. We reviewed hospital records and referrals of 232 GATA2 mutated individuals from 122 families to gather hematopoietic and syndromic features. Mutations were categorized by GATA2 protein effect: mutation after the 2nd Zinc-finger (Cterm, n=10); missense in the 2nd Zinc-Finger (ZF2, n=104); mutations producing stable truncated protein (Truncation, n=22); Null alleles (mRNA instability, large deletions, n=46); or Enhancer (n=50). Regression models for symptom onset identified earlier onset and increased hazard ratios (HR) between Truncation, Null or ZF2 mutations (13 years, HR 5.00; 17 years, 3.60; 22 years, 2.23 respectively) and Enhancer. Commonly mutated ZF2 amino acids stratified: R396 or T354 presented earlier with increased hazard ratios (16 years, HR 2.96; 19 years, HR 2.16) versus R398 (34 years). Mutation groups with median onset

GATA2 at 14: genotype-phenotype correlations

Key Points

Abstract

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