Authors
Shruthi Mohan, Tilda E Carlelycke, Ashwin Lakshman Koppayi, Taylor Walker, Eran Tallis, Amy M Trottier, Katherine R Calvo, Beatriz E Marciano, Amy P Hsu, Steven M Holland, Dennis D Hickstein, Marcin W Wlodarski, Emilia Kozyra, Matthew Collin, Christopher N Hahn, Anna L Brown, Piers Blombery, Ing Soo Tiong, Yamuna Kankanige, Lucy C Fox, Sioban B Keel, Marshall S Horwitz, Tom J Vulliamy, Inderjeet Dokal, Daniela P Mendes-de-Almeida, Rodrigo Tocantins Calado, Marcela Cavalcante de Andrade Silva, Elvira Deolinda Rodrigues Pereira Velloso, Courtney D DiNardo, Shai Izraeli, Joanne Yacobovich, Michaela Sherbeck, Julia T Warren, Minjie Luo, William J Smith, Zachary Hattig, Ryan J Stubbins, Simone K Feurstein, Panagiotis Baliakas, Xi Luo, Amagoia Ruiz Martin, Adam Gordon, Emery H Bresnick, Guimin Gao, Masha Kocherginsky, David Wu, Lucy A Godley
Published in
Blood. Aug 06, 2026. Epub Aug 06, 2026.
Abstract
Germline GATA2 deficiency is a pleiotropic condition 1-8 characterized by numerous phenotypes, including monocytopenia, immunodeficiency, microbial susceptibilities, and high rates of myeloid malignancies 1,8. Accurate curation of germline GATA2 variants is critical for patient care and requires well-defined phenotypes associated with GATA2 deficiency. The many phenotypes attributed to the condition render a simple description of GATA2 deficiency difficult, complicating the development of GATA2 variant curation rules. Therefore, the Myeloid Malignancy Variant Curation Expert Panel (MM-VCEP) sought to define GATA2 deficiency based on a statistical comparison of phenotype data. To do so, the MM-VCEP systematically analyzed phenotype data and applied statistical comparisons to define the phenotypic features of GATA2 deficiency to inform germline variant curation. The MM-VCEP assembled an international cohort of 339 people with clinically diagnosed GATA2 deficiency from 16 centers in seven countries. The 73 phenotypes of these individuals were compared statistically to those of control participants from the UK Biobank (UKBB). We compared single phenotypes as well as combinations of two, three, and four phenotypes in people with clinically diagnosed GATA2 deficiency to UKBB controls. We defined GATA2 deficiency as any of the 2,903 combinations of two or three phenotypes with log10Odds Ratio ≥3 (OR ≥ 1000). This definition of GATA2 deficiency will inform gene-specific phenotypic criteria used in GATA2 variant curation guidelines that will facilitate standardized variant curation by clinical laboratories worldwide.
PMID:
42561126
Bibliographic data and abstract were imported from PubMed on 07 Aug 2026.
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