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

Abstract

In this report it was presented 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. 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. 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 deafness-causing 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.

Keywords

• Hearing loss, SYNE4 gene, high-throughput DNA sequencing

References

1. 1. Kemperman MH, Hoefsloot LH, Cremers CW. Hearing loss and connexin 26. J R Soc Med 2002;95:171-7.
2. 2. Morton CC, Nance WE. Newborn hearing screening a silent revolution. N Engl J Med 2006;354:2151-64.
3. 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. 4. Finsterer J, Fellinger J. Nuclear and mitochondrial genes mutated in nonsyndromic impaired hearing. Int J Pediatr Otorhinolaryngol 2005;69:621-47.
5. 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. 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. 7. Starr DA, Han M. ANChors away: an actin based mechanism of nuclear positioning. J Cell Sci 2003;116:211-6.
8. 8. Dallos P. Cochlear amplification, outer hair cells and prestin. Curr Opin Neurobiol 2008;18:370-6.

9. 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. 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.