Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome

Auriculocondylar syndrome (ACS) is characterised by an ear malformation known as a “question mark ear” and variable under-development of the lower jaw. Recently, mutations in two genes, PLCB4 and GNAI3,were identified as the cause of ACS. We identified further mutations in these genes in a series of ACS patients, but not in patients with related craniofacial malformations. We identified a major hotspot of mutations affecting arginine 621 in PLCB4. In one patient we discovered a homozygous deletion within PLCB4, and in addition to ACS, he presented with central apnea, a disorder affecting central nervous system control of respiration, which has not been previously reported in ACS patients.Thus, our findings indicate that ACS can be an autosomal dominant or recessive condition according to the nature of the PLCB4 gene lesion and further emphasise the dominant negative effect of heterozygous missense mutations. (By Dr. Chris Gordon, http://jmg.bmj.com/content/early/2013/01/11/jmedgenet-2012-101331 )