GATA1 mutations in a cohort of Malaysian children with Down syndrome-associated myeloid disorder

Lum, Su Han; Choong, Soo Sin; Krishnan, Shekhar; Zeriouh, Mohamed; Ariffin, Hany

doi:10.11622/smedj.2016106

Cited by 5 publications

(4 citation statements)

References 26 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This was to specifically confirm all possible mutations, as some previous studies revealed a higher detection rate when exons 2 to 6 were examined. 11,13,19 However, we found mutations solely in exon 2; this was similar to the previous three studies, 11,13,19 which discovered them only at exons 2 and 3. There appears to be no benefit in performing the sequence for exons 4 to 6.…”

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

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

et al. 2019

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 91%

“…Peripheral blood and bone marrow results do not differ if there are over 10 to 20% blasts present in peripheral blood. Most studies 4,18,19 of TAM analyzed peripheral blood, like in ours.…”

Section: Discussionmentioning

confidence: 76%

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

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Both of the variations c.220G > A and c.49dupC are absent in the general population according to public databases (gnomAD, 1000 Genomes Project, and Exome Aggregation Consortium). Mutation c.220G > A has been reported in several research as pathogenic according to the ACMG guideline [29][30][31] . At the same amino acid c.220G > C (p.Val74Leu) change has been previously reported as pathogenic in the ClinVar database.…”

Section: Discussionmentioning

confidence: 99%

Prenatal diagnosis of Down syndrome combined with transient abnormal myelopoiesis in foetuses with a GATA1 gene variant: Two case reports

HUI

Liu

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Transient abnormal myelopoiesis (TAM) is a transient haematological disorder of Down syndrome that is characterised by leucocytosis, the presence of blasts, abnormal haematopoiesis and hepatosplenomegaly. It is usually diagnosed within 8 weeks of birth, and the median age of diagnosis is 3–7 days. Case presentation We report two cases of prenatally diagnosed TAM, both with male foetal onset. One case was a rare placental low percentage 21 trisomy mosiacism, resulting in the occurrence of a false negative NIPT. The final diagnosis was made at 36 weeks of gestation when ultrasound revealed significant enlargement of the foetal liver and spleen and an enlarged heart; the foetus eventually died in utero. We detected a placenta with a low percentage (5%-8%) of trisomy 21 mosiacism by CNV-seq and FISH. In another case, foetal oedema was detected by ultrasound at 31 weeks of gestation. Two foetuses were diagnosed with Down syndrome by chromosomal microarray analysis (CMA) via umbilical vein puncture and had significantly elevated cord blood leucocyte counts with large numbers of blasts. The GATA1 Sanger sequencing results suggested the presence of a [NM_002049.4(GATA1):c.220G > A (p. Val74Ile)] hemizygous variant and a [NM_002049.4(GATA1):c.49dupC(p. Gln17ProfsTer23)] hemizygous variant of the GATA1 gene in two cases. Conclusion It seems highly likely that these two identified mutations are the genetic cause of prenatal TAM in foetuses with Down syndrome.

show abstract

“…GATA1 sequencing identified the deletion of a single base (c.150delG) in exon 2, that caused a frameshift resulted in premature sequence termination (p.Ser51Alafs*86; Fig. 3) (15). …”

Section: Case Reportmentioning

confidence: 99%

Sometimes it is better to wait: First Italian case of a newborn with transient abnormal myelopoiesis and a favorable prognosis

Salvatori¹,

Foligno²,

Sirleto³

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Congenital leukemia is rare disease with an incidence of one to five cases per million births. Transient abnormal myelopoiesis (TAM), also called transient myeloproliferative disorder, is a pre-leukemia disorder that may occur in Down syndrome (DS) or non-DS infants. TAM may enter spontaneous remission; however, continual monitoring is required, as this disorder has been observed to develop into acute megakaryoblastic leukemia in 16–30% of cases. In the literature, 16 cases of TAM in non-DS infants have been reported. The case presented in the current study is, to the best of our knowledge, the first case of an Italian non-DS newborn presenting with clinical manifestations of acute leukemia at five days after birth, exhibiting a normal karyotype, trisomy 21 only in blast cells, and spontaneous remission. Chromosomal analyses on peripheral blood cells, bone marrow cells and dermal fibroblasts were conducted using a G-banding technique, and fluorescence in situ hybridization (FISH) was used to identify the critical regions of DS. Amplification of GATA binding protein 1 (GATA1) exon 2 genomic DNA was performed using polymerase chain reaction. Cytogenetic analysis of 50 peripheral blood cells and dermal fibroblasts from the patient revealed a normal karyotype: 46, XX. Conversely, cytogenetic analysis of the patient's bone marrow revealed an abnormal karyotype 47, XX+21. In order to investigate this result, FISH was performed, which identified the presence of three signals in 70% of the cells and two signals in 30% of bone marrow cells. GATA1 sequencing revealed the substitution of a single base (c.150delG) in exon 2. Seven months after the initial analysis, FISH and cytogenetic analyses of the stimulated/unstimulated peripheral blood cells and bone marrow cells were performed, revealing that each exhibited diploid signals, as observed in a normal karyotype.

show abstract

GATA1 mutations in a cohort of Malaysian children with Down syndrome-associated myeloid disorder

Cited by 5 publications

References 26 publications

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

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

Prenatal diagnosis of Down syndrome combined with transient abnormal myelopoiesis in foetuses with a GATA1 gene variant: Two case reports

Sometimes it is better to wait: First Italian case of a newborn with transient abnormal myelopoiesis and a favorable prognosis

Contact Info

Product

Resources

About