DOCK3-related neurodevelopmental syndrome: Biallelic intragenic deletion of DOCK3 in a boy with developmental delay and hypotonia

Am J Med Genet A. 2018 Jan;176(1):241-245. doi: 10.1002/ajmg.a.38517. Epub 2017 Nov 12.

Abstract

Dedicator of cytokinesis (DOCK) family are evolutionary conserved guanine nucleotide exchange factors (GEFs) for the Rho GTPases, Rac, and Cdc42. DOCK3 functions as a GEF for Rac1, and plays an important role in promoting neurite and axonal growth by stimulating actin dynamics and microtubule assembly pathways in the central nervous system. Here we report a boy with developmental delay, hypotonia, and ataxia due to biallelic DOCK3 deletion. Chromosomal single nucleotide polymorphism (SNP) microarray analysis detected a 170 kb homozygous deletion including exons 6-12 of the DOCK3 gene at 3p21.2. Symptoms of our proband resembles a phenotype of Dock3 knockout mice exhibiting sensorimotor impairments. Furthermore, our proband has clinical similarities with two siblings with compound heterozygous loss-of-function mutations of DOCK3 reported in [Helbig, Mroske, Moorthy, Sajan, and Velinov (); https://doi.org/10.1111/cge.12995]. Biallelic DOCK3 mutations cause a neurodevelopmental disorder characterized by unsteady gait, hypotonia, and developmental delay.

Keywords: SNP array; developmental delay; region of homozygosity.

Publication types

  • Case Reports

MeSH terms

  • Alleles
  • Child
  • Child, Preschool
  • Developmental Disabilities / diagnosis*
  • Developmental Disabilities / genetics*
  • Facies
  • Female
  • Genetic Association Studies*
  • Genotype
  • Guanine Nucleotide Exchange Factors / genetics*
  • Humans
  • Male
  • Mutation*
  • Nerve Tissue Proteins / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Sequence Deletion

Substances

  • DOCK3 protein, human
  • Guanine Nucleotide Exchange Factors
  • Nerve Tissue Proteins