GATA2 deficiency encompasses multiple diseases caused by pathogenic variants in the GATA2 gene: immunodeficiency 21 (MonoMAC, OMIM #614172), Emberger syndrome (OMIM #614038), a predisposition to myelodysplastic syndrome (MDS; OMIM #614286), and a predisposition to acute myeloid leukemia (AML; OMIM #601626).<\/p>\n<\/div>
Synonyms:<\/p>\n<\/div><\/div><\/div>
Emberger syndrome (MDS, lymphedema, and hearing loss)
\nMonoMAC syndrome (immunodeficiency 21)<\/p>\n<\/div><\/div><\/div><\/div>
Gene:<\/p>\n<\/div><\/div><\/div>
GATA2<\/i><\/p>\n<\/div><\/div><\/div><\/div> Gene \u00adproduct:<\/p>\n<\/div><\/div><\/div> GATA2<\/p>\n<\/div><\/div><\/div><\/div> Function:<\/p>\n<\/div><\/div><\/div> Transcription factor that regulates gene expression in hematopoietic cells. It contains two zinc finger (ZF) domains that mediate DNA binding and protein interactions.<\/p>\n<\/div><\/div><\/div><\/div> Pattern of inheritance:<\/p>\n<\/div><\/div><\/div> Autosomal dominant<\/p>\n<\/div><\/div><\/div><\/div> Prevalence:<\/p>\n<\/div><\/div><\/div> 7% of cases of primary MDS in children are based on a pathogenic variant GATA2<\/em>.<\/p>\n 72% of adults with MDS and monosomy 7 have a pathogenic variant GATA2<\/em>\u00a0(usually de novo<\/em>).<\/p>\n<\/div><\/div><\/div><\/div> Genotype-phenotype correlation:<\/p>\n<\/div><\/div><\/div> The most frequent mutations are truncating mutations before ZF2, missense mutations within ZF2, and non-coding variants in the +9.5kb regulatory region of GATA2. Penetrance:<\/p>\n<\/div><\/div><\/div> Approximately 90% up to the age of 60 for both hematological and immunological diseases
\nAll previously described germline mutations predispose to MDS\/AML, infectious diseases, and cytopenia, but only complete haploinsufficiency or GATA2 loss-of-function mutations predispose to lymphedemas.<\/p>\n<\/div><\/div><\/div><\/div>
\nMyeloid neoplasia occurs in approximately 70% of pathogenic variant carriers.<\/p>\n<\/div><\/div><\/div><\/div><\/div><\/div>