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A novel otoferlin splice-site mutation in siblings with auditory neuropathy spectrum disorder. Audiol Neurootol 2013;18(6):374-82



Pubmed ID


Pubmed Central ID




Scopus ID

2-s2.0-84885522606   15 Citations


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 JE


David R. Friedland MD Associate Director, Director, Chief, Professor in the Otolaryngology department at Medical College of Wisconsin
Joseph E. Kerschner MD Provost, Executive Vice President, Dean, Professor in the School of Medicine Administration department at Medical College of Wisconsin
Anne E. Kwitek PhD Professor in the Physiology department at Medical College of Wisconsin
Mark T. McNally PhD Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Christina Runge PhD Associate Provost, Chief, Professor in the Otolaryngology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Action Potentials
Cochlear Implantation
Cochlear Implants
Evoked Potentials, Auditory, Brain Stem
HEK293 Cells
Hearing Loss, Central
Hearing Loss, Sensorineural
Membrane Proteins
RNA Splice Sites
Speech Perception