More evidence on TRIO missense mutations in the spectrin repeat domain causing severe developmental delay and recognizable facial dysmorphism with macrocephaly

Neurogenetics. 2021 Jul;22(3):221-224. doi: 10.1007/s10048-021-00648-3. Epub 2021 May 19.

Abstract

TRIO is a Dbl family guanine nucleotide exchange factor (GEF) and an important regulator of neuronal development. Most truncating and missense variants affecting the Dbl homology domain of TRIO are associated with a neurodevelopmental disorder with microcephaly (MIM617061). Recently, de novo missense variants affecting the spectrin repeat region of TRIO were associated with a novel phenotype comprising severe developmental delay and macrocephaly (MIM618825). Here, we provide more evidence on this new TRIO-associated phenotype by reporting two severely affected probands with de novo missense variants in TRIO affecting the spectrin repeat region upstream of the typically affected GEF1 domain of the protein.

Keywords: Developmental delay; Facial dysmorphism; Genotype–phenotype correlation; Macrocephaly; Neurocognitive disorder; RAC1; TRIO.

MeSH terms

  • Guanine Nucleotide Exchange Factors / genetics*
  • Humans
  • Megalencephaly / genetics*
  • Microcephaly / genetics
  • Mutation, Missense / genetics*
  • Neurodevelopmental Disorders / genetics
  • Phenotype
  • Protein Serine-Threonine Kinases / genetics*
  • Spectrin / genetics*
  • Spectrin / metabolism

Substances

  • Guanine Nucleotide Exchange Factors
  • Spectrin
  • Protein Serine-Threonine Kinases
  • TRIO protein, human