A Novel Homozygous Frameshift Mutation in the PLCB4 Gene Associated with Auriculocondylar Syndrome 2 and Accompanied by Mild Intellectual Disability

Abstract

Auriculocondylar syndrome is a rare autosomal dominant or recessive disorder characterized by question-mark ears, a small mandibular condyle, and micrognathia. From a molecular perspective, auriculocondylar syndrome arises due to mutations in the PLCB4, GNAI3, and EDN1 genes that play roles in the endothelin signaling pathway. Here, we report a patient with findings of auriculocondylar syndrome and an additional mild intellectual disability. The patient's whole exome sequencing analyses revealed a novel homozygous frameshift mutation in the PLCB4 gene related to auriculocondylar syndrome Type 2. Our molecular studies indicated that this mutation caused a downregulation of PLCB4. This type of PLCB4 mutation has seldom been reported in auriculocondylar syndrome-2 patients and only 2 of them have had neurodevelopmental anomalies, as in our patient. We think that this study supports the possibility of intellectual disability in individuals with a homozygous truncating variant in the PLCB4 gene and contributes to the literature.