Frequency of Usher syndrome in two pediatric populations: Implications for genetic screening of deaf and hard of hearing children

Abstract

Purpose: Usher syndrome is a major cause of genetic deafness and blindness. The hearing loss is usually congenital and the retinitis pigmentosa is progressive and first noticed in early childhood to the middle teenage years. Its frequency may be underestimated. Newly developed molecular technologies can detect the underlying gene mutation of this disorder early in life providing estimation of its prevalence in at risk pediatric populations and laying a foundation for its incorporation as an adjunct to newborn hearing screening programs.

Methods: A total of 133 children from two deaf and hard of hearing pediatric populations were genotyped first for GJB2/6 and, if negative, then for Usher syndrome. Children were scored as positive if the test revealed > or =1 pathogenic mutations in any Usher gene.

Results: Fifteen children carried pathogenic mutations in one of the Usher genes; the number of deaf and hard of hearing children carrying Usher syndrome mutations was 15/133 (11.3%). The population prevalence was estimated to be 1/6000.

Conclusion: Usher syndrome is more prevalent than has been reported before the genome project era. Early diagnosis of Usher syndrome has important positive implications for childhood safety, educational planning, genetic counseling, and treatment. The results demonstrate that DNA testing for Usher syndrome is feasible and may be a useful addition to newborn hearing screening programs.

Figure 1

Proposed paradigm for screening D/HOH children for Usher syndrome. The patient is first tested GJB2/6. If no GJB2/6 mutation is observed, testing continues for the most commonly occurring Usher mutations. Any positive test refers to the presence of ≥ 1 pathogenic mutations which, when only 1 pathogenic allele is observed, should be confirmed by a search for the second allele. The ‘Future Tests’ box refers to the probable incorporation of tests for other genetic types of hearing loss such as for the genes SLC26A4, OTOF, etc. The ‘confirm by sequencing’ step includes a search for a second mutation, if needed.