| Autor: |
Su Han Lum, Soo Sin Choong, Krishnan, Shekhar, Mohamed, Zulqarnain, Ariffin, Hany, Lum, Su Han, Choong, Soo Sin |
| Předmět: |
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| Zdroj: |
Singapore Medical Journal; Jun2016, Vol. 57 Issue 6, p320-324, 5p |
| Abstrakt: |
Introduction: Children with Down syndrome (DS) are at increased risk of developing distinctive clonal myeloid disorders, including transient abnormal myelopoiesis (TAM) and myeloid leukaemia of DS (ML-DS). TAM connotes a spontaneously resolving congenital myeloproliferative state observed in 10%-20% of DS newborns. Following varying intervals of apparent remission, a proportion of children with TAM progress to develop ML-DS in early childhood. Therefore, TAM and ML-DS represent a biological continuum. Both disorders are characterised by recurring truncating somatic mutations of the GATA1 gene, which are considered key pathogenetic events.Methods: We herein report, to our knowledge, the first observation on the frequency and nature of GATA1 gene mutations in a cohort of Malaysian children with DS-associated TAM (n = 9) and ML-DS (n = 24) encountered successively over a period of five years at a national referral centre.Results: Of the 29 patients who underwent GATA1 analysis, GATA1 mutations were observed in 15 (51.7%) patients, including 6 (75.0%) out of 8 patients with TAM, and 9 (42.9%) of 21 patients with ML-DS. All identified mutations were located in exon 2 and the majority were sequence-terminating insertions or deletions (66.7%), including several hitherto unreported mutations (12 out of 15).Conclusion: The low frequency of GATA1 mutations in ML-DS patients is unusual and potentially indicates distinctive genomic events in our patient cohort. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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