Germline de novo alterations of RUNX1T1 in individuals with neurodevelopmental and congenital anomalies
Summary: Runt-related transcription factor 1 translocated to 1 (RUNX1T1; also known as eight-twenty-one [ETO]) encodes a transcription regulator for hematopoietic genes and is well known for its involvement in hematologic malignancies, particularly acute myeloid leukemia (AML). However, its role in...
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Elsevier
2025-01-01
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| Series: | HGG Advances |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666247724001246 |
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| author | Erfan Aref-Eshghi Katherine J. Anderson Lauren Boulay Kathleen Brown Jessica Duis Christine A. Giummo Jessica Ogawa Deanna Alexis Carere Elizabeth A. Normand Yaping Qian Kirsty McWalter Erin Torti |
| author_facet | Erfan Aref-Eshghi Katherine J. Anderson Lauren Boulay Kathleen Brown Jessica Duis Christine A. Giummo Jessica Ogawa Deanna Alexis Carere Elizabeth A. Normand Yaping Qian Kirsty McWalter Erin Torti |
| author_sort | Erfan Aref-Eshghi |
| collection | DOAJ |
| description | Summary: Runt-related transcription factor 1 translocated to 1 (RUNX1T1; also known as eight-twenty-one [ETO]) encodes a transcription regulator for hematopoietic genes and is well known for its involvement in hematologic malignancies, particularly acute myeloid leukemia (AML). However, its role in congenital disease is less understood. This study provides detailed clinical and molecular information on three cases exhibiting neurodevelopmental and congenital anomalies with germline de novo alterations in RUNX1T1. One case features a de novo nonsense variant in the 5′ region of the gene (c.106C>T p.Gln36Ter), while the other two harbor de novo missense variants in the C terminus end (c.1234G>A p.Gly412Arg and c.1561C>T p.His521Tyr). Common features across cases include craniofacial dysmorphism and neurodevelopmental issues, including developmental delay, learning disabilities, attention-deficit hyperactivity disorder, and autism. This study, in conjunction with previously reported germline disruptions of RUNX1T1, provides evidence supporting the role of germline RUNX1T1 variation in human congenital neurodevelopmental disorders. |
| format | Article |
| id | doaj-art-c2f349dfe2e048f4801d494abc5fbe23 |
| institution | DOAJ |
| issn | 2666-2477 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | HGG Advances |
| spelling | doaj-art-c2f349dfe2e048f4801d494abc5fbe232025-08-20T02:39:28ZengElsevierHGG Advances2666-24772025-01-016110038410.1016/j.xhgg.2024.100384Germline de novo alterations of RUNX1T1 in individuals with neurodevelopmental and congenital anomaliesErfan Aref-Eshghi0Katherine J. Anderson1Lauren Boulay2Kathleen Brown3Jessica Duis4Christine A. Giummo5Jessica Ogawa6Deanna Alexis Carere7Elizabeth A. Normand8Yaping Qian9Kirsty McWalter10Erin Torti11GeneDx, LLC, Gaithersburg, MD 20877, USAUniversity of Vermont Larner College of Medicine, Department of Pediatrics, Division of Clinical Genetics, Burlington, VT 05401, USADepartment of Pediatrics, Section of Genetics and Metabolism, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Pediatrics, Section of Genetics and Metabolism, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, CO 80045, USARareDiseaseDoc, LLC, Aurora, CO, USAUniversity of Vermont Larner College of Medicine, Department of Pediatrics, Division of Clinical Genetics, Burlington, VT 05401, USACase Western Reserve University School of Medicine/Rainbow Babies and Children’s Hospital, Department of Genetics and Genome Sciences, Cleveland, OH 44106, USAGeneDx, LLC, Gaithersburg, MD 20877, USAGeneDx, LLC, Gaithersburg, MD 20877, USAGeneDx, LLC, Gaithersburg, MD 20877, USAGeneDx, LLC, Gaithersburg, MD 20877, USAGeneDx, LLC, Gaithersburg, MD 20877, USA; Corresponding authorSummary: Runt-related transcription factor 1 translocated to 1 (RUNX1T1; also known as eight-twenty-one [ETO]) encodes a transcription regulator for hematopoietic genes and is well known for its involvement in hematologic malignancies, particularly acute myeloid leukemia (AML). However, its role in congenital disease is less understood. This study provides detailed clinical and molecular information on three cases exhibiting neurodevelopmental and congenital anomalies with germline de novo alterations in RUNX1T1. One case features a de novo nonsense variant in the 5′ region of the gene (c.106C>T p.Gln36Ter), while the other two harbor de novo missense variants in the C terminus end (c.1234G>A p.Gly412Arg and c.1561C>T p.His521Tyr). Common features across cases include craniofacial dysmorphism and neurodevelopmental issues, including developmental delay, learning disabilities, attention-deficit hyperactivity disorder, and autism. This study, in conjunction with previously reported germline disruptions of RUNX1T1, provides evidence supporting the role of germline RUNX1T1 variation in human congenital neurodevelopmental disorders.http://www.sciencedirect.com/science/article/pii/S2666247724001246RUNX1T1clinical exome sequencingneurodevelopmental disorderautismcongenital anomaliescandidate gene |
| spellingShingle | Erfan Aref-Eshghi Katherine J. Anderson Lauren Boulay Kathleen Brown Jessica Duis Christine A. Giummo Jessica Ogawa Deanna Alexis Carere Elizabeth A. Normand Yaping Qian Kirsty McWalter Erin Torti Germline de novo alterations of RUNX1T1 in individuals with neurodevelopmental and congenital anomalies HGG Advances RUNX1T1 clinical exome sequencing neurodevelopmental disorder autism congenital anomalies candidate gene |
| title | Germline de novo alterations of RUNX1T1 in individuals with neurodevelopmental and congenital anomalies |
| title_full | Germline de novo alterations of RUNX1T1 in individuals with neurodevelopmental and congenital anomalies |
| title_fullStr | Germline de novo alterations of RUNX1T1 in individuals with neurodevelopmental and congenital anomalies |
| title_full_unstemmed | Germline de novo alterations of RUNX1T1 in individuals with neurodevelopmental and congenital anomalies |
| title_short | Germline de novo alterations of RUNX1T1 in individuals with neurodevelopmental and congenital anomalies |
| title_sort | germline de novo alterations of runx1t1 in individuals with neurodevelopmental and congenital anomalies |
| topic | RUNX1T1 clinical exome sequencing neurodevelopmental disorder autism congenital anomalies candidate gene |
| url | http://www.sciencedirect.com/science/article/pii/S2666247724001246 |
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