2. Academic Validation
  3. A recurrent de novo CTBP1 mutation is associated with developmental delay, hypotonia, ataxia, and tooth enamel defects

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

  • Neurogenetics. 2016 Jul;17(3):173-8. doi: 10.1007/s10048-016-0482-4.
David B Beck 1,  Megan T Cho 2,  Francisca Millan 2,  Carin Yates 2,  Mark Hannibal 3,  Bridget O'Connor 3,  Marwan Shinawi 4,  Anne M Connolly 5,  Darrel Waggoner 6,  Sara Halbach 6,  Brad Angle 7,  Victoria Sanders 7,  Yufeng Shen 8,  Kyle Retterer 2,  Amber Begtrup 2,  Renkui Bai 2,  Wendy K Chung 9
Affiliations

Affiliations

  • 1 Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, NY, USA.
  • 2 GeneDx, Gaithersburg, MD, USA.
  • 3 Department of Pediatrics and Communicable Diseases, Division of Pediatric Genetics, Metabolism & Genomic Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
  • 4 Department of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • 5 Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
  • 6 Department of Pediatrics, University of Chicago, Chicago, IL, USA.
  • 7 Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • 8 Departments of Systems Biology and Biomedical Informatics, Columbia University Medical Center, New York, NY, USA.
  • 9 Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, NY, USA. [email protected].
PMID: 27094857 DOI: 10.1007/s10048-016-0482-4
Abstract

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.

Keywords

Ataxia; CTBP1; Chromatin; Developmental delay; Enamel defects; Hypotonia; Whole exome sequencing.

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