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The phenotype spectrum of our genotyped patients diagnosed with Usher syndrome
type IIC
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András Végh , Rita Vámos , Péter István Takács , Ágnes Takács , Barbara Besztercei ,
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Ditta Zobor , Krisztina Knézy , Balázs Varsányi , Zoltán Zsolt Nagy , Viktória Szabó
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1 Semmelweis Egyetem, Szemészeti Klinika, Budapest
2 Ganglion Orvosi Központ, Pécs
Introduction: Usher syndrome is an autosomal recessive hereditary disease that
ophthalmologically manifests itself in symptomatic retinitis pigmentosa. Usher syndrome has
three types. Along with sight loss, bilateral hear loss is a typical symptom that appears during
adolescence in type II. Not all cases involve hear impairment.
In type II, the significant narrowing of the visual field develops in the third decade, followed by
the damage of colour vision and central sight. In the background of its pathogenesis, biallelic
mutations of ADGRV1, USH2A and WHRN genes have been reported. The aim of the authors
is to precisely assess patients with hearing loss and retinitis pigmentosa, as well as to perform
their genotyping.

The ADGRV1 gene encodes a G protein coupled receptor with seven transmembrane domains
that binds calcium and is expressed in the central nervous system. Its mutation causes Usher
syndrome type IIC in that the symptoms of retinopathy occur around the age of 30 years. Some
publications suggest that the mutation of ADGRV1 causes milder clinical symptoms than the
mutation of USH2A, whereas other studies found no difference between the phenotype of the
two gene mutations.

Materials and Methods: The authors examined over 300 patients at the Department of
Ophthalmology at Semmelweis University with standard methods and multimodal imaging.
Genotyping of patients with characteristic symptoms was performed with new generation
sequencing (Retinal Dystrophy NGS Panel).

Results: We identified 18 patients with type II Usher syndrome of whom 15 had the biallelic
mutations in gene USH2A, 3 had biallelic mutations in gene ADGRV1. The mutation of
ADGRV1 in our patients caused mild to severe symptoms, their best corrected visual acuity
varied between hand movement and 1.0. The onset of the manifestation of the disease showed
large differences as the retinal dystrophy occurred at infancy with excessive nystagmus in the
case of a couple of siblings, whereas in another case it started with nyctalopia at the age of 18
years.

Conclusion: With detailed clinical, imaging and electrophysiological examinations as well as
with genotyping, we documented both the phenotype and the genotype of our patients. In two
cases we found more severe manifestation than the cases reported in the literature that
indicates the presence of other factors as well, thus we plan the segregation analysis of the
whole family and the revalidation of other marked genes in the case of the siblings and their
parents.