A novel missense variant of the GNAI3 gene and recognisable morphological characteristics of the mandibula in ARCND1

J Hum Genet. 2021 Oct;66(10):1029-1034. doi: 10.1038/s10038-021-00915-z. Epub 2021 Mar 15.

Abstract

Auriculocondylar syndrome (ARCND) is an autosomal monogenic disorder characterised by external ear abnormalities and micrognathia due to hypoplasia of the mandibular rami, condyle and coronoid process. Genetically, three subtypes of ARCND (ARCND1, ARCND2 and ARCND3) have been reported. To date, five pathogenic variants of GNAI3 have been reported in ARCND1 patients. Here, we report a novel variant of GNAI3 (NM_006496:c.807C>A:p.(Asn269Lys)) in a Japanese girl with micrognathia using trio-based whole exome sequencing analysis. The GNAI3 gene encodes a heterotrimeric guanine nucleotide-binding protein. The novel variant locates the guanine nucleotide-binding site, and the substitution was predicted to interfere with guanine nucleotide-binding by in silico structural analysis. Three-dimensional computer tomography scan, or cephalogram, displayed severely hypoplastic mandibular rami and fusion to the medial and lateral pterygoid plates, which have been recognised in other ARCND1 patients, but have not been described in ARCND2 and ARCND3, suggesting that these may be distinguishable features in ARCND1.

Publication types

  • Case Reports

MeSH terms

  • Child, Preschool
  • Ear / abnormalities*
  • Ear / diagnostic imaging
  • Ear / pathology
  • Ear Diseases / diagnosis
  • Ear Diseases / diagnostic imaging
  • Ear Diseases / genetics*
  • Ear Diseases / pathology
  • Exome Sequencing
  • Female
  • GTP-Binding Protein alpha Subunits, Gi-Go / genetics*
  • Humans
  • Mandible / diagnostic imaging*
  • Mandible / pathology
  • Micrognathism / diagnosis
  • Micrognathism / diagnostic imaging
  • Micrognathism / genetics*
  • Micrognathism / pathology
  • Mutation, Missense / genetics
  • Pedigree
  • Phenotype

Substances

  • GNAI3 protein, human
  • GTP-Binding Protein alpha Subunits, Gi-Go

Supplementary concepts

  • Auriculo-condylar syndrome