Strc-KO Mouse

Strc, encoding the protein stereocilin, is located on chromosome 15q15.3. The loss of the stereocilin protein induces the loss of connection between outer hair cells and tectorial membrane, affecting outer hair cells (OHCs) function, involving deficits of active cochlear frequency selectivity and amplifier functions despite normal inner hair cells [5].

Mutations in the STRC gene, inducing DFNB16, are a major cause of mild-moderate autosomal recessive non-syndromic hearing loss (ARNSHL). The pooled prevalence of DFNB16 in GJB2-negative patients with hearing loss was 4.08% (95% CI: 0.0289-0.0573), and the proportion of STRC variants in the mild-moderate hearing loss group was 14.36% [1]. In Japanese hearing loss patients, the prevalence of STRC-associated hearing loss was 2.77% (276/9956) [2]. In Europe, mutations in STRC account for 16% of the autosomal recessive cases of non-syndromic hearing impairment [3]. In pediatric patients with biallelic pathogenic STRC mutations, all had bilateral, symmetric sensorineural hearing loss (SNHL), with 58% showing some degree of progressive HL [4]. Behavioral studies in human subjects with STRC loss-of-function mutations showed impaired spectral ripple discrimination, a trend of impaired frequency resolution, and impaired speech-in-noise perception compared to normal-hearing listeners, yet better than cochlear implant listeners [5]. In the Czech population, STRC gene mutations are an important cause of autosomal recessive non-syndromic hearing loss, probably the second most common cause of DFNB, with large copy number variations (CNVs) more frequent than point mutations [6,7]. Also, patients with biallelic STRC gene deletions had a 39% prevalence of recurrent benign paroxysmal positional vertigo (BPPV), with an early age of onset [8].

In conclusion, Strc is crucial for maintaining the connection between outer hair cells and tectorial membrane in the cochlea, playing a significant role in auditory function. Mutations in Strc are strongly associated with mild-moderate autosomal recessive non-syndromic hearing loss, and may also be related to BPPV. Understanding Strc and its mutations helps in better genetic counseling and clinical management of related hearing disorders.

References:

1. Han, Shuang, Zhang, Dejun, Guo, Yingyuan, Fu, Zeming, Guan, Guofang. 2021. Prevalence and Characteristics of STRC Gene Mutations (DFNB16): A Systematic Review and Meta-Analysis. In Frontiers in genetics, 12, 707845. doi:10.3389/fgene.2021.707845. https://pubmed.ncbi.nlm.nih.gov/34621290/

2. Nishio, Shin-Ya, Usami, Shin-Ichi. 2022. Frequency of the STRC-CATSPER2 deletion in STRC-associated hearing loss patients. In Scientific reports, 12, 634. doi:10.1038/s41598-021-04688-5. https://pubmed.ncbi.nlm.nih.gov/35022556/

3. Del Castillo, Ignacio, Morín, Matías, Domínguez-Ruiz, María, Moreno-Pelayo, Miguel A. 2022. Genetic etiology of non-syndromic hearing loss in Europe. In Human genetics, 141, 683-696. doi:10.1007/s00439-021-02425-6. https://pubmed.ncbi.nlm.nih.gov/35044523/

4. Simi, Andrea, Perry, Julia, Schindler, Emma, Kawai, Kosuke, Kenna, Margaret. 2021. Audiologic Phenotype and Progression in Pediatric STRC-Related Autosomal Recessive Hearing Loss. In The Laryngoscope, 131, E2897-E2903. doi:10.1002/lary.29680. https://pubmed.ncbi.nlm.nih.gov/34111299/

5. Benoit, Charlotte, Carlson, Ryan J, King, Mary-Claire, Horn, David L, Rubinstein, Jay T. 2023. Behavioral characterization of the cochlear amplifier lesion due to loss of function of stereocilin (STRC) in human subjects. In Hearing research, 439, 108898. doi:10.1016/j.heares.2023.108898. https://pubmed.ncbi.nlm.nih.gov/37890241/

6. Marková, Simona Poisson, Brožková, Dana Šafka, Laššuthová, Petra, Staněk, David, Seeman, Pavel. . STRC Gene Mutations, Mainly Large Deletions, are a Very Important Cause of Early-Onset Hereditary Hearing Loss in the Czech Population. In Genetic testing and molecular biomarkers, 22, 127-134. doi:10.1089/gtmb.2017.0155. https://pubmed.ncbi.nlm.nih.gov/29425068/

7. Plevova, Pavlina, Paprskarova, Martina, Tvrda, Petra, Slavkovsky, Rastislav, Mrazkova, Eva. . STRC Deletion is a Frequent Cause of Slight to Moderate Congenital Hearing Impairment in the Czech Republic. In Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 38, e393-e400. doi:10.1097/MAO.0000000000001571. https://pubmed.ncbi.nlm.nih.gov/28984810/

8. Achard, Sophie, Campion, Margaux, Parodi, Marine, Loundon, Natalie, Marlin, Sandrine. 2023. Recurrent Benign Paroxysmal Positional Vertigo in DFNB16 Patients with Biallelic STRC Gene Deletions. In Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 44, e241-e245. doi:10.1097/MAO.0000000000003825. https://pubmed.ncbi.nlm.nih.gov/36764706/