Journal article
A Homozygous SLITRK6 Nonsense Mutation is Associated With Progressive Auditory Neuropathy in Humans
The Laryngoscope, v 124(3), pp E95-E103
Mar 2014
PMID: 23946138
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Objectives/Hypothesis SLITRK family proteins control neurite outgrowth and regulate synaptic development. In mice, Slitrk6 plays a role in the survival and innervation of sensory neurons in the inner ear, vestibular apparatus, and retina, and also influences axial eye length. We provide the first detailed description of the auditory phenotype in humans with recessive SLITRK6 deficiency.
Study DesignProspective observational case study.
MethodsNine closely related Amish subjects from an endogamous Amish community of Pennsylvania underwent audiologic and vestibular testing. Single nucleotide polymorphism microarrays were used to map the chromosome locus, and Sanger sequencing or high-resolution melt analysis were used to confirm the allelic variant.
ResultsAll nine subjects were homozygous for a novel nonsense variant of SLITRK6 (c.1240C>T, p.Gln414Ter). Adult patients had high myopia. The 4 oldest SLITRK6 c.1240C>T homozygotes had absent ipsilateral middle ear muscle reflexes (MEMRs). Distortion product otoacoustic emissions (DPOAEs) were absent in all ears tested and the cochlear microphonic (CM) was increased in amplitude and duration in young patients and absent in the two oldest subjects. Auditory brainstem responses (ABRs) were dys-synchronised bilaterally with no reproducible waves I, III, or V at high intensities. Hearing loss and speech reception thresholds deteriorated symmetrically with age, which resulted in severe-to-profound hearing impairment by early adulthood. Vestibular evoked myogenic potentials were normal in three ears and absent in one.
Conclusion Homozygous SLITRK6 c.1240C>T (p.Gln414Ter) nonsense mutations are associated with high myopia, cochlear dysfunction attributed to outer hair cell disease, and progressive auditory neuropathy.
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Details
- Title
- A Homozygous SLITRK6 Nonsense Mutation is Associated With Progressive Auditory Neuropathy in Humans
- Creators
- Thierry Morlet - Community Health Systems - Dupont HospitalMindy R. Rabinowitz - Thomas Jefferson University HospitalLiesl R. Looney - Community Health Systems - Dupont HospitalTammy Riegner - Community Health Systems - Dupont HospitalL. Ashleigh Greenwood - Community Health Systems - Dupont HospitalEric A. Sherman - Swarthmore CollegeNathan Achilly - Franklin & Marshall CollegeAnni Zhu - Franklin & Marshall CollegeEstelle Yoo - Community Health Systems - Dupont HospitalRobert C. O'Reilly - duPont Hosp Children, Dept Otolaryngol Head & Neck Surg, Wilmington, DE USARobert N. Jinks - Franklin & Marshall CollegeErik G. Puffenberger - Clinic for Special ChildrenAdam Heaps - Clinic for Special ChildrenHolmes Morton - Clinic for Special ChildrenKevin A. Strauss - Clinic for Special Children
- Publication Details
- The Laryngoscope, v 124(3), pp E95-E103
- Publisher
- Wiley
- Number of pages
- 9
- Grant note
- Center for Research on Women and Newborn Health P20GM103464 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) 8P20GM103464 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P20RR020173 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) 52006294; 52007538 / Howard Hughes Medical Institute (HHMI); Howard Hughes Medical Institute Connect-Care3
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Audiology - Distance
- Web of Science ID
- WOS:000331374300006
- Scopus ID
- 2-s2.0-84894492788
- Other Identifier
- 991022169839304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Medicine, Research & Experimental
- Otorhinolaryngology