A novel otoferlin splice-site mutation in siblings with auditory neuropathy spectrum disorder. Audiol Neurootol 2013;18(6):374-82
Date
10/19/2013Pubmed ID
24135434Pubmed Central ID
PMC3877672DOI
10.1159/000354978Scopus ID
2-s2.0-84885522606 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
We characterize a novel otoferlin mutation discovered in a sibling pair diagnosed with auditory neuropathy spectrum disorder and investigate auditory nerve function through their cochlear implants. Genetic sequencing revealed a homozygous mutation at the otoferlin splice donor site of exon 28 (IVS28 + 1G>T) in both siblings. Functional investigation showed that the intronic sequence between exons 28 and 29 was retained in the mutated minigenes that were expressed in 293T cells. Auditory nerve compound action potential recovery functions in the siblings demonstrated different rates of neural recovery, with sibling AN1 showing rapid recovery (1.14 ms) and AN2 showing average recovery (0.78 ms) compared to subjects with sensorineural hearing loss (average: adults 0.71 ms, children 0.85 ms). Differences in neural recovery were consistent with speech perception differences between the siblings. Genotype information may indicate site of lesion in hearing loss; however, additional, as yet, unknown factors may impact clinical outcomes and must be considered.
Author List
Runge CL, Erbe CB, McNally MT, Van Dusen C, Friedland DR, Kwitek AE, Kerschner JEAuthors
Joseph E. Kerschner MD Emeritus Dean, Professor in the Otolaryngology department at Medical College of WisconsinAnne E. Kwitek PhD Professor in the Physiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Action PotentialsAdult
Cochlear Implantation
Cochlear Implants
Evoked Potentials, Auditory, Brain Stem
Female
HEK293 Cells
Hearing Loss, Central
Hearing Loss, Sensorineural
Homozygote
Humans
Membrane Proteins
RNA Splice Sites
Siblings
Speech Perception
