The development of high sensitive diagnostic methods for Leukemia in Down syndrome
Date Issued
2015
Date
2015
Author(s)
Wu, Yueh-Eo
Abstract
Background Down syndrome (DS) is the most common disorders associated with intelligent disabilities in aneuploidy disorders with an incidence of one in 800 live births. Patients with DS present with symptoms of multi-systemic manifestations, including short stature, mental retardation, malformations, congenital heart disease, congenital gastrointestinal and genitourinary tract abnormalities, endocrine dysfunction, Leukemia and Leukemoid reaction. DS patients had 10-20 times higher risk to develop Leukemia, especially the Acute Megakaryoblastic Leukemia (AMKL) which is even 500 times higher. The cause of Leukemia in DS is considered to be related to the GATA1 mutation, resulting in a temporary myeloproliferative disorders and acute megakaryocytic leukemia (AML). DS and leukemia mostly GATA1 gene mutation. Because of patient blood sampling is difficult, so we hope to establish a method to use blood spots (Dried blood spot; referred DBS) to extract DNA sequencing to detect gene GATA1. Method DNA was extracted from dried blood spots were proceeded into polymerase chain reaction and Sanger sequencing method for GATA1 mutation analysis. This study analyzed three groups of patients. The first group was a retrospective analysis of 24 patients, of whom nine had myeloproliferative disorders (TMD 3 people; AMKL 6 people), 13 DS patients without Leukemia and two AMLK patients but not DS. The second group was prospectively analyzed 24 DS patients in our hospital. The third group of the sample was from 39 Mongolia DS patients without Leukemia. Result Retrospective analysis of 24 patients revealed eight DS patients had positive GATA1 mutations, with the detection rate was 100% (3/3) in DS-TMD; and 83.3% (5/6) in DS-AMLK respectively. The prospective analysis of 24 patients in our hospital showed only one positive for GATA1 mutation in a 3 year-old boy with the detection rate of 4.2%. In 39 Mongolian samples, none was detected to have GATA1 mutation (0%). Conclusion From this study, we established the method to analyze GATA1 mutation from DBS samples. In the future, the utilization of this method could help in the early diagnosis of Leukemia in DS patients, providing an early treatment to achieve better outcome.
Subjects
Down syndrome
Leukemia
GATA1 gene
Mutation analysis
Dried blood spot
Type
thesis
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