Mustafa TEKİN, John MASTERSON, Busegül YILDIRIM, Ece GÖKKAYA, Suna Tokgöz YILMAZ

A Novel Variant in SYNE4 Confirms its Causative Role in Sensorineural Hearing Loss

Background: Hearing loss is the most common sensory deficit with many genetic and environmental underpinnings. While causative DNA variants have been identified in over 100 genes, most deafnesscausing variants are rare, apart from a few exceptions. A single SYNE4 variant co-segregating with hearing loss has recently been reported in two Middle-Eastern families. Case Report: In this report we present two members of a family with non-syndromic high frequency sensorineural hearing loss who are homozygous for a novel pathogenic SYNE4 variant c.129-1G>T. Conclusion: This case report provides supportive evidence for the causative role of SYNE4 variants in hearing loss by presenting an additional family with a novel DNA variant.

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1. Kemperman MH, Hoefsloot LH, Cremers CW. Hearing loss and connexin 26. J R Soc Med 2002;95:171-7.
2. Morton CC, Nance WE. Newborn hearing screening a silent revolution. N Engl J Med 2006;354:2151-64.
3. Vozzi D, Morgan A, Vuckovic D, D'Eustacchio A, Abdulhadi K, Rubinato E, et al. Hereditary hearing loss: a 96 gene targeted sequencing protocol reveals novel alleles in a series of Italian and Qatari patients. Gene 2014;542:209-16.
4. Finsterer J, Fellinger J. Nuclear and mitochondrial genes mutated in nonsyndromic impaired hearing. Int J Pediatr Otorhinolaryngol 2005;69:621-47.
5. Atik T, Bademci G, Diaz-Horta O, Blanton SH, Tekin M. Whole-exome sequencing and its impact in hereditary hearing loss. Genet Res (Camb) 2015;97:e4.
6. Bademci G, Foster J, Mahdieh N, Bonyadi M, Duman D, Cengiz FB, et al. Comprehensive Analysis via Exome Sequencing Uncovers Genetic Etiology in Autosomal Recessive Non-Syndromic Deafness in a Large Multiethnic Cohort. Genet Med 2016;18:364-71.
7. Starr DA, Han M. ANChors away: an actin based mechanism of nuclear positioning. J Cell Sci 2003;116:211-6.
8. Dallos P. Cochlear amplification, outer hair cells and prestin. Curr Opin Neurobiol 2008;18:370-6.
9. Horn HF, Brownstein Z, Lenz DR, Shivatzki S, Dror AA, Dagan-Rosenfeld O, et al. The LINC complex is essential for hearing. J Clin Invest 2013;123:740-50.
10. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405-24.