Prenatal diagnosis of Down syndrome combined with transient abnormal myelopoiesis in foetuses with a GATA1 gene variant: two case reports
Abstract Background Down syndrome myeloid hyperplasia includes transient abnormal myelopoiesis (TAM) and the myeloid leukemia associated with Down syndrome (ML-DS). The mutation of GATA1 gene is essential in the development of Down syndrome combined with TAM or ML-DS. Some patients with TAM are asym...
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Molecular Cytogenetics |
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| Online Access: | https://doi.org/10.1186/s13039-023-00658-w |
| _version_ | 1797556231783579648 |
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| author | Hui Tang Jingjing Hu Ling Liu Lijuan Lv Jian Lu Jiexia Yang Jiaqi Lu Zhenhui Chen Chaoxiang Yang Dan Chen Jintao Fu Jing Wu |
| author_facet | Hui Tang Jingjing Hu Ling Liu Lijuan Lv Jian Lu Jiexia Yang Jiaqi Lu Zhenhui Chen Chaoxiang Yang Dan Chen Jintao Fu Jing Wu |
| author_sort | Hui Tang |
| collection | DOAJ |
| description | Abstract Background Down syndrome myeloid hyperplasia includes transient abnormal myelopoiesis (TAM) and the myeloid leukemia associated with Down syndrome (ML-DS). The mutation of GATA1 gene is essential in the development of Down syndrome combined with TAM or ML-DS. Some patients with TAM are asymptomatic and may also present with severe manifestations such as hepatosplenomegaly and hydrops. Case presentation We report two cases of prenatally diagnosed TAM. 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 Copy Number Variation Sequencing (CNV-seq) and Fluorescence in situ hybridization (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 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. |
| first_indexed | 2024-03-10T16:59:52Z |
| format | Article |
| id | doaj.art-6275bd30a41d48e39dd0a7309fb94b4e |
| institution | Directory Open Access Journal |
| issn | 1755-8166 |
| language | English |
| last_indexed | 2024-03-10T16:59:52Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cytogenetics |
| spelling | doaj.art-6275bd30a41d48e39dd0a7309fb94b4e2023-11-20T11:01:11ZengBMCMolecular Cytogenetics1755-81662023-10-011611810.1186/s13039-023-00658-wPrenatal diagnosis of Down syndrome combined with transient abnormal myelopoiesis in foetuses with a GATA1 gene variant: two case reportsHui Tang0Jingjing Hu1Ling Liu2Lijuan Lv3Jian Lu4Jiexia Yang5Jiaqi Lu6Zhenhui Chen7Chaoxiang Yang8Dan Chen9Jintao Fu10Jing Wu11Gentic Medical Center, Guangdong Women and Children HospitalGentic Medical Center, Guangdong Women and Children HospitalGentic Medical Center, Guangdong Women and Children HospitalGentic Medical Center, Guangdong Women and Children HospitalGentic Medical Center, Guangdong Women and Children HospitalGentic Medical Center, Guangdong Women and Children HospitalGentic Medical Center, Guangdong Women and Children HospitalLaboratory Department, Guangdong Women and Children HospitalRadiology Department, Guangdong Women and Children HospitalUltrasound Department, Guangdong Women and Children HospitalPathology Department, Guangdong Women and Children HospitalGentic Medical Center, Guangdong Women and Children HospitalAbstract Background Down syndrome myeloid hyperplasia includes transient abnormal myelopoiesis (TAM) and the myeloid leukemia associated with Down syndrome (ML-DS). The mutation of GATA1 gene is essential in the development of Down syndrome combined with TAM or ML-DS. Some patients with TAM are asymptomatic and may also present with severe manifestations such as hepatosplenomegaly and hydrops. Case presentation We report two cases of prenatally diagnosed TAM. 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 Copy Number Variation Sequencing (CNV-seq) and Fluorescence in situ hybridization (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 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.https://doi.org/10.1186/s13039-023-00658-wTransient abnormal myelopoiesisDown syndromeTrisomy 21GATA1Prenatal diagnosis |
| spellingShingle | Hui Tang Jingjing Hu Ling Liu Lijuan Lv Jian Lu Jiexia Yang Jiaqi Lu Zhenhui Chen Chaoxiang Yang Dan Chen Jintao Fu Jing Wu Prenatal diagnosis of Down syndrome combined with transient abnormal myelopoiesis in foetuses with a GATA1 gene variant: two case reports Molecular Cytogenetics Transient abnormal myelopoiesis Down syndrome Trisomy 21 GATA1 Prenatal diagnosis |
| title | Prenatal diagnosis of Down syndrome combined with transient abnormal myelopoiesis in foetuses with a GATA1 gene variant: two case reports |
| title_full | Prenatal diagnosis of Down syndrome combined with transient abnormal myelopoiesis in foetuses with a GATA1 gene variant: two case reports |
| title_fullStr | Prenatal diagnosis of Down syndrome combined with transient abnormal myelopoiesis in foetuses with a GATA1 gene variant: two case reports |
| title_full_unstemmed | Prenatal diagnosis of Down syndrome combined with transient abnormal myelopoiesis in foetuses with a GATA1 gene variant: two case reports |
| title_short | Prenatal diagnosis of Down syndrome combined with transient abnormal myelopoiesis in foetuses with a GATA1 gene variant: two case reports |
| title_sort | prenatal diagnosis of down syndrome combined with transient abnormal myelopoiesis in foetuses with a gata1 gene variant two case reports |
| topic | Transient abnormal myelopoiesis Down syndrome Trisomy 21 GATA1 Prenatal diagnosis |
| url | https://doi.org/10.1186/s13039-023-00658-w |
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