Speech and language delay in a patient with WDR4 mutations

Eur J Med Genet. 2018 Aug;61(8):468-472. doi: 10.1016/j.ejmg.2018.03.007. Epub 2018 Mar 26.

Abstract

Primordial dwarfism (PD) is mainly characterized by growth deficiency with heterogeneous phenotypes. A group of genes are known to be associated with PD or PD-related syndrome. WD repeat domain 4 (WDR4) is recently reported to be responsible for PD. Here we report a 6-year-old boy from a non-consanguineous couple with motor and speech delay as well as intellectual disability. Whole exome sequencing (WES) identified a missense mutation (NM_033661.4:c.491A > C; p.(Asp164Ala)) and a small insertion (NM_033661.4:c.940dupC; p.(Leu314Profs*16)) of WDR4 in this patient. Two novel mutations confirmed by Sanger sequencing are from father and mother respectively according to a recessive inheritance pattern. Asp164Ala located in functional region is predicted to be deleterious by two kinds of algorithm. The small insertion causing a frameshift mutation leads to truncated protein. In this study, we present two novel WDR4 mutations responsible for PD in a 6-year-old patient, expanding the molecular and phenotype spectrum of WDR4-related PD.

Keywords: Mutation; Primordial dwarfism (PD); WDR4; Whole-exome sequencing.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Dwarfism / genetics*
  • Dwarfism / pathology
  • Frameshift Mutation
  • GTP-Binding Proteins / genetics*
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Language Development Disorders / genetics*
  • Language Development Disorders / pathology
  • Male
  • Mutation, Missense
  • Phenotype*
  • Syndrome

Substances

  • WDR4 protein, human
  • GTP-Binding Proteins