Using a multi-omic approach, we identified three novel pathogenic variants in two Usher syndrome genes (USH2A and ADGRV1) in cases initially referred for isolated vision or hearing loss.
The mutations found in our study not only broaden the mutation spectrum of ADGRV1, but also provide assistances for future genetic diagnosis and treatment for Usher syndrome patients.
We isolated a mouse strain with hearing loss from inbred mice with retinal degeneration and established it as a recombinant inbred strain with a spontaneous mutation in Adgrv1, the human Usher syndrome 2C gene.
Next generation sequencing-based molecular diagnosis of retinitis pigmentosa: identification of a novel genotype-phenotype correlation and clinical refinements.
Interaction of MEF2C with the deleted febrile seizure (FEB4) and juveline myoclonic epilepsy (EJM4) loci plus the G-protein receptor (GPR98/MASS1/Usher syndrome) gene may moderate the phenotype, perhaps through common regulation by calcium.
Consistent with these clinical findings, the five subjects with USH carried a haplotype linked to the USH2C locus, whereas the two subjects with nonsyndromic hearing loss did not.
The identification of additional VLGR1 mutations to test whether a phenotype/genotype correlation exists, akin to that shown for other Usher syndrome disease genes, is warranted.