Usher Syndrome Gene Panel
Dr. rer. biol. hum. S. Chahrokh-Zadeh
The Usher syndrome, a group of clinically and genetically heterogeneous, autosomal recessive diseases, is the main cause (> 50%) of deaf-blindness. The three major subtypes USH1, USH2, and USH3 are mainly differentiated by the severity and progression of the hearing loss and the presence of vestibular dysfunction. So far 12 genes and one modifier gene (PDZD7) have been identified.
The most common subtype is USH2 (moderate to severe hearing loss, rather late onset (after puberty) of retinitis pigmentosa (RP), and normal vestibular function). Most of the mutations (USH2A; 57-79%) can be found in the USH2A gene.
USH1 constitutes about 30-40% of all USH types and is the most severe form characterized by profound, congenital deafness, prepubertal onset of progressive RP, and vestibular dysfunction. The classification of the subtypes based on clinical data is insufficient due to the fact that, even if identical mutations a present, the phenotypic variability can be high. Thus far 9 loci and 6 genes are known: MYO7A (USH1B; 53-63% of all USH1), USH1C (USH1C; 1-15%), CDH23 (USH1D; 7-20%), PCDH15 (USH1F; 7-12%), USH1G (USH1G) und CIB2 (USH1J).
All coding exons and their flanking intronic sequences from the genes in the gene panel arrhythmogenic diseases are analyzed either by Sanger sequencing or by next generation sequencing (NGS).