A recurrent de novo CTBP1 mutation is associated with developmental delay, hypotonia, ataxia, and tooth enamel defects

Neurogenetics - Tập 17 - Trang 173-178 - 2016
David B. Beck1, Megan T. Cho2, Francisca Millan2, Carin Yates2, Mark Hannibal3, Bridget O’Connor3, Marwan Shinawi4, Anne M. Connolly5, Darrel Waggoner6, Sara Halbach6, Brad Angle7, Victoria Sanders7, Yufeng Shen8, Kyle Retterer2, Amber Begtrup2, Renkui Bai2, Wendy K. Chung1
1Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, USA
2GeneDx, Gaithersburg, USA
3Department of Pediatrics and Communicable Diseases, Division of Pediatric Genetics, Metabolism & Genomic Medicine, University of Michigan Medical School, Ann Arbor, USA
4Department of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine, St. Louis, USA
5Department of Neurology, Washington University School of Medicine, St. Louis, USA
6Department of Pediatrics, University of Chicago, Chicago, USA
7Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, USA
8Departments of Systems Biology and Biomedical Informatics, Columbia University Medical Center, New York, USA

Tóm tắt

Exome sequencing is an effective way to identify genetic causes of etiologically heterogeneous conditions such as developmental delay and intellectual disabilities. Using exome sequencing, we have identified four patients with similar phenotypes of developmental delay, intellectual disability, failure to thrive, hypotonia, ataxia, and tooth enamel defects who all have the same de novo R331W missense variant in C-terminal binding protein 1 (CTBP1). CTBP1 is a transcriptional regulator critical for development by coordinating different regulatory pathways. The R331W variant found in these patients is within the C-terminal portion of the PLDLS (Pro-Leu-Asp-Leu-Ser) binding cleft, which is the domain through which CTBP1, interacts with chromatin-modifying enzymes and mediates chromatin-dependent gene repression pathways. This is the first report of mutations within CTBP1 in association with any human disease.

Tài liệu tham khảo

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