Characterization of an induced pluripotent stem cell line (UMi040-A) bearing an auditory neuropathy spectrum disorder-associated variant in TMEM43.

Hearing loss is one of the most common sensory disorders. TMEM43 is expressed in cochlear glia-like supporting cells (GLSs) and is known to be associated with late-onset auditory neuropathy spectrum disorder (ANSD) and progressive hearing loss. Here, we describe the derivation of an induced pluripotent stem cell (iPSC) line from a patient lymphoblastoid cell line (LCL) carrying a single heterozygous nonsense variant (p.Arg372Ter (c.1114C > T)) in TMEM43 that leads to a truncated protein lacking the 4th transmembrane domain. This cell line can serve as a tool for disease modelling and development of therapeutic approaches to restore inner ear function.

Success rates in restoring hearing loss in patients with chronic otitis media: A systematic review.

OBJECTIVE: To assess the effectiveness of tympanoplasty in treating chronic otitis media-related hearing loss, published literature was systematically reviewed to determine the clinical success rate of tympanoplasty at restoring hearing in chronic otitis media patients at a minimum follow-up period of 12-months. DATA SOURCES: PubMed, Embase and the Cochrane Library. METHODS: Two independent reviewers performed literature searches. Publications reporting long-term (≥12-month) hearing outcomes and complications data on adult and pediatric patients with chronic otitis media were included and assessed for risk of bias and strength of evidence. To assess how tympanoplasty influences long-term hearing outcomes, data on pure tone audiometry (air-bone gap) and complications were extracted and synthesized. RESULTS: Thirty-nine studies met the inclusion criteria. Data from 3162 patients indicated that 14.0% of patients encountered postoperative complications. In adult patients, mean weighted air-bone gap data show closure from 26.5 dB hearing level (HL) (preoperatively) to 16.1 dB HL (postoperatively). In studies that presented combined adult and pediatric data, the mean preoperative air-bone gap of 26.7 dB HL was closed to 15.4 dB HL. In 1370 patients with synthesizable data, 70.7% of patients had a postoperative air-bone gap ˂ 20 dB HL at long-term follow-up. Finally, subgroup analysis identified that mean improvement in ABG closure for patients with and without cholesteatoma was 10.0 dB HL and 12.4 dB HL, respectively. CONCLUSION: In patients with chronic otitis media, tympanoplasty successfully closed the air-bone gap to within 20 dB HL in 7/10 cases and had an overall complication rate of 14.0%. LEVEL OF EVIDENCE: 2a.