De novo variants in KLF7 are a potential novel cause of developmental delay/intellectual disability, neuromuscular and psychiatric symptoms

Clin Genet. 2018 May;93(5):1030-1038. doi: 10.1111/cge.13198. Epub 2018 Jan 25.

Abstract

Due to small numbers of reported patients with pathogenic variants in single genes, the phenotypic spectrum associated with genes causing neurodevelopmental disorders such as intellectual disability (ID) and autism spectrum disorder is expanding. Among these genes is KLF7 (Krüppel-like factor 7), which is located at 2q33.3 and has been implicated in several developmental processes. KLF7 has been proposed to be a candidate gene for the phenotype of autism features seen in patients with a 2q33.3q34 deletion. Herein, we report 4 unrelated individuals with de novo KLF7 missense variants who share similar clinical features of developmental delay/ID, hypotonia, feeding/swallowing issues, psychiatric features and neuromuscular symptoms, and add to the knowledge about the phenotypic spectrum associated with KLF7 haploinsufficiency.

Keywords: KLF7; Krüppel-like transcription factors; autism; clinical diagnostics; intellectual disability; whole-exome sequencing; zinc finger DNA-binding protein.

MeSH terms

  • Adolescent
  • Autism Spectrum Disorder / genetics*
  • Autism Spectrum Disorder / pathology
  • Autism Spectrum Disorder / psychology
  • Child
  • Child, Preschool
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / pathology
  • Developmental Disabilities / psychology
  • Exome Sequencing
  • Female
  • Genetic Predisposition to Disease
  • Haploinsufficiency / genetics
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Intellectual Disability / psychology
  • Kruppel-Like Transcription Factors / genetics*
  • Male
  • Mutation, Missense / genetics

Substances

  • KLF7 protein, human
  • Kruppel-Like Transcription Factors