New germline GATA1 variant in females with anemia and thrombocytopenia

Author(s)

Costa Melo Svidnicki, Maria Carolina ^[1] ; Ferreira Filho, Moises Alves ^[1] ; Brandao, Marcelo Mendes ^[2] ; dos Santos, Marielza ^[3] ; Dias, Renata de Oliveira ^[4] ; Tavares, Renato Sampaio ^[5] ; Assis-Mendonca, Guilherme Rossi ^[6] ; Traina, Fabiola ^{[1, 7]} ; Olalla Saad, Sara Teresinha ^[1]

Affiliation

^[1] Univ Estadual Campinas, Hematol & Transfus Med Ctr, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Mol Biol & Genet Engeneering Ctr, Campinas, SP - Brazil

^[3] Gen Hosp Doutor Francisco Ayres, Palmas, Tocantins - Brazil

^[4] Univ Goias, Inst Biol Sci, Goiania, Go - Brazil

^[5] Univ Goias, Clin Hosp, Hematol Div, Goiania, Go - Brazil

^[6] Univ Estadual Campinas, Fac Med Sci, Dept Pathol, Campinas, SP - Brazil

^[7] Ribeirao Preto Med Sch, Dept Med Images Hematol & Clin Oncol, Univ Sao Paulo, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: BLOOD CELLS MOLECULES AND DISEASES; v. 88, MAY 2021.
• Web of Science Citations: 0

Abstract

Familial forms of bone marrow defects are rare disorders and description of new cases are valuable opportunities to clarify the molecular machinery that triggers hematopoiesis and blood formation, as well as risk to malignant transformation. We investigated the genetic scenario and possible patterns of transmission in a rare case of familial myeloid disorder with a history of exposure to pesticides. Blood counts of two proband sisters, age 41 and 42, revealed mild anemia, neutrophilia and thrombocytopenia with bone marrow finding mimicking primary myelofibrosis in the cellular phase. We analyzed the coding regions of 78 myeloid neoplasms-related genes and 16 encoding xenobiotic metabolizing genes using Next-Generation Sequencing. The GATA1 variant c.788C > T, p.T263M, located in the C-terminal zinc finger domain of GATA1, was detected in the DNA of the two sisters. The screening of the other kindreds also revealed the p.T263M variant in the mother and two daughters with the same bone marrow disorder. This is the first report of an alteration in the GATA1 CF domain causing anemia, thrombocytopenia and megakaryocyte proliferation with mild myelofibrosis, correlating a new GATA1 germline variant with myeloid disorder. (AU)

• FAPESP's process: 17/21801-2 - Predictors of severity and new treatments for bone marrow neoplasias
• Grantee: Sara Teresinha Olalla Saad
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 15/18574-9 - Screening of mutations related to hereditary anemias using NGS-Targeted sequencing panel
• Grantee: Maria Carolina Costa Melo Svidnicki
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 11/51959-0 - Biology of neoplastic diseases of bone marrow
• Grantee: Sara Teresinha Olalla Saad
• Support type: Research Projects - Thematic Grants