GATA1 mutations in a cohort of Malaysian children with Down syndrome-associated myeloid disorder
Singapore medical journal
;
: 320-324, 2016.
Article
Dans Anglais
| WPRIM
| ID: wpr-296409
ABSTRACT
<p><b>INTRODUCTION</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>The low frequency of GATA1 mutations in ML-DS patients is unusual and potentially indicates distinctive genomic events in our patient cohort.</p>
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Orientation vers un spécialiste
/
Induction de rémission
/
Leucémie myéloïde
/
Exons
/
Études de cohortes
/
Délétion de gène
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Syndrome de Down
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Génomique
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Facteur de transcription GATA-1
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Génétique
Type d'étude:
Etude d'étiologie
/
Etude d'incidence
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Étude observationnelle
/
Étude pronostique
/
Facteurs de risque
Limites du sujet:
Femelle
/
Humains
/
Mâle
/
Nouveau-né
Pays comme sujet:
Asie
langue:
Anglais
Texte intégral:
Singapore medical journal
Année:
2016
Type:
Article
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