A de novo CSDE1 variant causing neurodevelopmental delay, intellectual disability, neurologic and psychiatric symptoms in a child of consanguineous parents

Am J Med Genet A. 2022 Jan;188(1):283-291. doi: 10.1002/ajmg.a.62494. Epub 2021 Sep 14.


CSDE1 encodes the cytoplasmic cold shock domain-containing protein E1 (CSDE1), which is highly conserved across species and functions as an RNA-binding protein involved in translationally coupled mRNA turnover. CSDE1 displays a bidirectional role: promoting and repressing the translation of RNAs but also increasing and decreasing the abundance of RNAs. Preclinical studies highlighted an involvement of CSDE1 in different forms of cancer. Moreover, CSDE1 is highly expressed in human embryonic stem cells and plays a role in neuronal migration and differentiation. A genome-wide association study suggested CSDE1 as a potential autism-spectrum disorder risk gene. A multicenter next generation sequencing approach unraveled likely causative heterozygous variants in CSDE1 in 18 patients, identifying a new autism spectrum disorder-related syndrome consisting of autism, intellectual disability, and neurodevelopmental delay. Since then, no further patients with CSDE1 variants have been reported in the literature. Here, we report a 9.5-year-old girl from a consanguineous family of Turkish origin suffering from profound delayed speech and motor development, moderate intellectual disability, neurologic and psychiatric symptoms as well as hypoplasia of corpus callosum and mildly reduced brain volume on brain magnetic resonance imaging associated with a recurrent de novo mutation in CSDE1 (c.367C > T; p.R123*) expanding the phenotypical spectrum associated with pathogenic CSDE1 variants.

Keywords: anxiety; developmental delay; intellectual disability; muscle weakness; pathological laughter and cry.

Publication types

  • Case Reports
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autism Spectrum Disorder* / diagnosis
  • Autism Spectrum Disorder* / genetics
  • Child
  • Consanguinity
  • DNA-Binding Proteins / genetics
  • Female
  • Genome-Wide Association Study
  • Humans
  • Intellectual Disability* / diagnosis
  • Intellectual Disability* / genetics
  • Intellectual Disability* / pathology
  • Mutation
  • Parents
  • RNA-Binding Proteins / genetics


  • CSDE1 protein, human
  • DNA-Binding Proteins
  • RNA-Binding Proteins