Table 1.

Molecular Genetic Testing Used in Usher Syndrome Type II (USH2)

Gene 1, 2USH2 SubtypeProportion of USH2 Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 3 Detected by Method
Sequence analysis 4Gene-targeted deletion/duplication analysis 5
ADGRV1 USH2C6.6%-19% 6>90% 73/49 individuals 8
USH2A USH2A57%-79% 6>90% 7, 96%-9% 10, 11
WHRN USH2D0%-9.5% 6>95% 7None reported 7
Unknown 12, 13NA

Genes are listed in alphabetic order.


See Molecular Genetics for information on variants detected in this gene.


Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.


Several deep intronic variants outside of the exon and splice junction regions typically included in standard sequencing have been observed, especially in USH2A [Vaché et al 2012, Liquori et al 2016, Baux et al 2017, Mansard et al 2021, Daich Varela et al 2023].


By screening for duplications/deletions, Steele-Stallard et al [2013] found a second USH2A pathogenic variant in 26% (6/23) of individuals for whom only one disease-causing allele had been found by sequencing.


A fourth locus associated with Usher syndrome type II has been provisionally mapped to 15q in a consanguineous Tunisian family [Ben Rebeh et al 2008].


To date, PDZD7 pathogenic variants have not been shown to cause Usher syndrome but may act as modifiers of the retinal phenotype in individuals with USH2A-related USH2 [Ebermann et al 2010]. Additionally, an individual with USH2 and compound heterozygous pathogenic variants in USH2A and PDZD7 and another affected individual with compound heterozygous variants in ADGRV1 and PDZD7 were reported, leading to the suggestion of digenic inheritance [Ebermann et al 2010].

From: Usher Syndrome Type II

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