CNV = copy number variant; STRC-HL = STRC-related autosomal recessive hearing loss

See Table A. Genes and Databases for chromosome locus and protein.

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

Provided figures are estimates based on Shearer et al [2014], Han et al [2021], and Shubina-Oleinik et al [2021].

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

Provided figures are estimates based on Shearer et al [2014], Amr et al [2018], Han et al [2021], Nishio & Usami [2022], and data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020].

Supplementing standard next-generation sequencing (NGS) methods with long-range PCR-based sequencing or NGS assays increases the yield of pathogenic STRC sequencing variants by eliminating pseudogene contamination.

Most reported STRC deletions/duplications are large and detectable by chromosomal microarray analysis (CMA). CMA uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including STRC) that cannot be detected by sequence analysis. The ability to determine the size of the deletion/duplication depends on the type of microarray used and the density of probes in the 15q15.3 region. CMA designs in current clinical use targets the 15q15.3 region. Smaller deletions/duplications involving single or multiple exons within the gene (which are less frequently seen than contiguous gene copy number abnormalities) are also detectable using quantitative PCR or multiplex ligation-dependent probe amplification (MLPA). MLPA is an effective method to also eliminate pseudogene contamination and is frequently used to evaluate STRC CNVs. Exome and genome sequencing with CNV detection may be able to detect deletions/duplications.

Provided figures are estimates based on Mandelker et al [2014], Shearer et al [2014], Han et al [2021], Nishio & Usami [2022].

Based on published reports to date, biallelic contiguous gene deletions involving STRC and CATSPER2 are estimated to be the most prevalent genotype in individuals with STRC-HL [Nishio & Usami 2022].