Missense variants at the p.Arg225 residue in ARHGEF40 identified in individuals with multiple congenital anomalies and developmental delay.

Abstract

The ARHGEF40 gene, also known as SOLO, encodes a RhoA-targeting guanine nucleotide exchange factor (GEF) and is currently considered a candidate gene with a potential relationship to disease. Our laboratory has confirmed variants at position p.Arg225 of the ARHGEF40 protein in multiple unrelated individuals with a phenotype including dysmorphic features, congenital anomalies and neurodevelopmental abnormalities. Here, we provide genetic and phenotypic information for two individuals harboring de novo variants at p.Arg225 and sharing a highly similar phenotype. This report suggests a relationship between variants at this amino acid position and autosomal dominant disease, and further studies will be needed to characterize this disease-gene relationship and elucidate the disease mechanism.