Usher syndrome: clinical and genetic variation in the Russian Federation

Abstract

Usher syndrome (USH) is a rare genetic disorder characterized by a combination of sensorineural hearing loss, retinitis pigmentosa, and, in some cases, vestibular disorders. It is inherited mainly by autosomal recessive type. Also, there are forms with digenic types of inheritance. The incidence of the disease in the world varies from 3 to 6.2 per 100,000 people. Currently, there are 4 clinical types of USH associated with 16 genes. The genes encode proteins involved in the formation and maintenance of the functions of stereocilia of inner ear hair cells and retinal receptors.

Data from patients with genetically confirmed USH were used to analyze the results. The total sample is 69 individuals from 63 families. Routine clinical and high-tech instrumental, molecular-genetic methods were applied, and medical and genetic counseling was carried out.

Neurosensory hearing loss was detected in all patients, but the earliest and most severe form is found in type 1 USH. Vestibular disorders are most common in type 1. Clouding of the lens and the presence of cystic macular edema are characteristic of type 2 USH. Retinitis pigmentosa was found in all patients in the sample. However, there was an atypical form of PR with central retinal zone lesion.

Molecular genetic diagnostics performed by high-throughput sequencing of the target gene panel and/or complete exome and/or genome, multiplex ligase-dependent amplification (MLPA), Sanger family segregation analysis allowed to determine the most frequent types of USH – type 1 and type 2 (52% and 42%, respectively). In type 1, the most frequent were pathogenic variants in MYO7A gene, in type 2 – in USH2A. Type 3 USH is the least frequent type (6%). The results obtained necessitate further study of this problem.