A familial PLCB4 mutation causing auriculocondylar syndrome 2 with variable severity

Eur J Med Genet. 2020 Jun;63(6):103917. doi: 10.1016/j.ejmg.2020.103917. Epub 2020 Mar 19.

Abstract

Auriculocondylar syndrome (ARCND, MIM #614669, #602483, and #615706); also known as ''question-mark ear syndrome'' or ''dysgnathia complex'', is a rare craniofacial malformation of first and second branchial arches with a prevalence of <1/1,000,000. It is characterized by a distinctive auricular malformation (question mark ear (QME)) and highly variable mandibular anomalies. Variants found in PLCB4, GNAI3, and in EDN1 genes are responsible for >90% of tested ARCND patients. Whole exome sequencing in a multigenerational Egyptian kindred with high intrafamilial variability revealed a known heterozygous missense variant in PLCB4 (NM_000933.3:c.1862G>A:p.(Arg621His)). This report increases the number of molecularly characterized ARCND patients to 29 and emphasizes the highly variable clinical presentation within families.

Keywords: ARCND; Familial; Mandibular to maxillary transformation; PLCB4; Variability.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Ear / abnormalities*
  • Ear / pathology
  • Ear Diseases / genetics*
  • Ear Diseases / pathology
  • Endothelin-1 / genetics
  • Female
  • GTP-Binding Protein alpha Subunits, Gi-Go / genetics
  • Humans
  • Male
  • Mutation*
  • Pedigree
  • Phenotype*
  • Phospholipase C beta / genetics*

Substances

  • Endothelin-1
  • PLCB4 protein, human
  • Phospholipase C beta
  • GNAI3 protein, human
  • GTP-Binding Protein alpha Subunits, Gi-Go

Supplementary concepts

  • Auriculo-condylar syndrome