Purpose:
Usher syndrome is an autosomal recessive disorder characterized by hearing and vision loss. Usher syndrome
is divided into three clinical subclasses (type 1, type 2, and type 3), which differ in terms of the severity and progression
of hearing loss and the presence or absence of vestibular symptoms. Usher syndrome is defined by significant genetic
heterogeneity, with at least 12 distinct loci described and 9 genes identified. This study aims to provide a molecular
epidemiology report of Usher syndrome in Italy.
Methods:
Molecular data have been obtained on 75 unrelated Italian patients using the most up-to date technology
available for the screening of Usher syndrome gene mutations, i.e., the genotyping microarray developed by Asper Biotech
(Tartu, Estonia), which simultaneously investigates 612 different marker positions using the well established arrayed
primer extension methodology (APEX).
Results:
Using this method, we found that 12% of cases (9 out of 75) harbored homozygous or compound heterozygous
mutations in the gene positions analyzed, whereas 20% (15 out of 75) of the patients were characterized by the presence
of only one mutated allele based on the positions analyzed. One patient was found to be compound heterozygous for
mutations in two different genes and this represents an example of possible digenic inheritance in Usher syndrome. A
total of 66.6% of cases (50 out of 75) were found to be completely negative for the presence of Usher syndrome gene
mutations in the detected positions. Mutations detected by the array were confirmed by direct sequencing.
Conclusions:
These findings highlight the efficacy of the APEX-based genotyping approach in the molecular assessment
of Usher patients, suggesting the presence of alleles not yet identified and/or the involvement of additional putative genes
that may account for the pathogenesis of Usher syndrome.
