Two Novel GATA1 Mutations in Transient Abnormal Myelopoiesis of Thai Neonates with Down Syndrome

Kanokporn Chukua; Chayanont Netsawang; Kittipoom Padungthai; Thanitchet Khetkham; Piyaporn Chokevittaya; Onapinya Poonjearansilp; Sariya Prachuktum; Sudatip Kositamongkol; Wiliporn Techasatit; Phakatip Silapamongkolkul; Wallee Satayasai; Tasama Pusongchai; Pacharapan Surapolchai; Kitiwan Rojnueangnit

doi:10.1055/s-0039-1696971

Two Novel GATA1 Mutations in Transient Abnormal Myelopoiesis of Thai Neonates with Down Syndrome

J Pediatr Genet. 2019 Dec;8(4):187-192. doi: 10.1055/s-0039-1696971. Epub 2019 Sep 11.

Authors

Affiliations

¹ Faculty of Medicine, Thammasat University, Pathum Thani, Thailand.
² Divison of Forensic Medicine, Thammasat University Hospital, Pathum Thani, Thailand.
³ Department of Pediatrics, Division of Genetics, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand.

Abstract

Children with Down syndrome (DS) are 150 times more likely to develop acute myeloid leukemia (ML-DS), compared with those without. One risk factor is transient abnormal myelopoiesis (TAM). Somatic truncating GATA1 mutations are found in most TAM patients and are markers for future ML-DS. We identified two novel frameshift mutations in our seven newborns with DS and TAM: a heterozygous mutation of 17 nucleotide duplication (c.154_170 dup) and a heterozygous 9-nucleotide deletion combined with a 2-nucleotide insertion (c.150_158delins CT). Both mutations introduced a truncated GATA1 protein. Thus, neonates with DS and TAM require frequent ML-DS monitoring.

Keywords: Down syndrome; GATA1 mutation; transient abnormal myelopoiesis.