In:
Clinical and Experimental Otorhinolaryngology, Korean Society of Otorhinolaryngology-Head and Neck Surgery, Vol. 13, No. 2 ( 2020-05-01), p. 113-122
Abstract:
Objectives. We, herein, report two novel 〈 i 〉 USH2A 〈 /i 〉 variants from two unrelated Korean families and their clinical phenotypes, with attention to severe or more than severe sensorineural hearing loss (SNHL).Methods. Two postlingually deafened subjects (SB237-461, M/46 and SB354-692, F/34) with more than severe SNHL and also with suspicion of Usher syndrome type II (USH2) were enrolled. A comprehensive audiological and ophthalmological assessments were evaluated. We conducted the whole exome sequencing and subsequent pathogenicity prediction analysis.Results. We identified the following variants of 〈 i 〉 USH2A 〈 /i 〉 from the two probands manifesting more than severe SNHL and retinitis pigmentosa (RP): compound heterozygosity for a nonsense (c.8176C 〉 T: p.R2723X) and a missense variant (c.1823G 〉 A: p.C608Y) in SB237, and compound heterozygosity for two frameshift variants (c.14835delT: p.S4945fs & c.13112_13115delAAAT: p.G4371fs) in SB354. Based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines, two novel variants, c.1823G 〉 A: p.C608Y and c.14835delT: p.Ser4945fs, can be classified as “uncertain significance” and “pathogenic,” respectively. The audiogram exhibited more than severe SNHL and a down-sloping configuration, necessitating cochlear implantation. The ophthalmic examinations revealed typical features of RP. Interestingly, one proband (SB 354-692) carrying two truncating compound heterozygous variants exhibited more severe hearing loss than the other proband (SB 237-461), carrying one truncation with one missense variant.Conclusion. Our results provide insight on the expansion of audiological spectrum encompassing more than severe SNHL in Korean subjects harboring 〈 i 〉 USH2A 〈 /i 〉 variants, suggesting that 〈 i 〉 USH2A 〈 /i 〉 should also be included in the candidate gene of cochlear implantation. A specific combination of 〈 i 〉 USH2A 〈 /i 〉 variants causing truncating proteins in both alleles could demonstrate more severe audiological phenotype than that of 〈 i 〉 USH2A 〈 /i 〉 variants carrying one truncating mutation and one missense mutation, suggesting a possible genotype-phenotype correlation. The understanding of audiological complexity associated with 〈 i 〉 USH2A 〈 /i 〉 will be helpful for genetic counseling and treatment starategy.
Type of Medium:
Online Resource
ISSN:
1976-8710
,
2005-0720
DOI:
10.21053/ceo.2019.00990
Language:
English
Publisher:
Korean Society of Otorhinolaryngology-Head and Neck Surgery
Publication Date:
2020
detail.hit.zdb_id:
2491719-9
