Analysis of GATA1 mutations and leukemogenesis in newborns with Down syndrome

• Published in: Genetics and molecular research 2013-10, Vol.12 (4), p.4630-4638
• Main Authors: Queiroz, L B, Lima, B D, Mazzeu, J F, Camargo, R, Córdoba, M S, Q Magalhães, I, Martins-de-Sá, C, Ferrari, I
• Format: Article
• Language: English
• Subjects: Base Sequence; DNA Mutational Analysis; Down Syndrome - drug therapy; Down Syndrome - genetics; Female; Frameshift Mutation; GATA1 Transcription Factor - genetics; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Infant; Infant, Newborn; Leukemia, Myeloid - drug therapy; Leukemia, Myeloid - genetics; Male; Myeloproliferative Disorders - drug therapy; Myeloproliferative Disorders - genetics; Treatment Outcome
• ISSN: 1676-5680; 1676-5680
• DOI: 10.4238/2013.October.18.1

It has been reported that patients with Down syndrome (DS) frequently develop transient myeloproliferative disorder (TMD) and less commonly myeloid leukemia in DS (ML-DS). We examined the pathogenetic relationship of these conditions with somatic mutations of the GATA1 gene in children with both TMD and ML-DS. To determine the incidence of GATA1 mutations in a cohort of DS patients and the applicability of these mutations as a clonal marker to detect minimal residual disease, we screened 198 samples of 169 patients with DS for mutations in GATA1 exon 2 by direct sequencing. Novel mutations were detected in four of the 169 DS patients (2 with TMD and 2 with ML-DS). We examined spontaneous remission and response to therapy in TMD and ML-DS patients and concluded that these mutations can be used as stable markers in PCR analysis to monitor these events.