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. Epub 2016 Apr 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alcohol Oxidoreductases / genetics*
  • Ataxia / complications
  • Ataxia / genetics*
  • Child
  • DNA-Binding Proteins / genetics*
  • Dental Enamel / pathology*
  • Developmental Disabilities / complications
  • Developmental Disabilities / genetics*
  • Exome Sequencing
  • Female
  • Humans
  • Intellectual Disability / complications
  • Intellectual Disability / genetics
  • Male
  • Muscle Hypotonia / complications
  • Muscle Hypotonia / genetics*
  • Mutation, Missense*
  • Young Adult


  • DNA-Binding Proteins
  • Alcohol Oxidoreductases
  • C-terminal binding protein