A homozygous SLITRK6 nonsense mutation is associated with progressive auditory neuropathy in humans.

Autor: Morlet T; Auditory Physiology and Psychoacoustics Research Laboratory, duPont Hospital for Children, Wilmington, Delaware, U.S.A., Rabinowitz MR, Looney LR, Riegner T, Greenwood LA, Sherman EA, Achilly N, Zhu A, Yoo E, O'Reilly RC, Jinks RN, Puffenberger EG, Heaps A, Morton H, Strauss KA
Jazyk: angličtina
Zdroj: The Laryngoscope [Laryngoscope] 2014 Mar; Vol. 124 (3), pp. E95-103. Date of Electronic Publication: 2013 Dec 17.
DOI: 10.1002/lary.24361
Abstrakt: 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 Design: Prospective observational case study.
Methods: Nine 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.
Results: All 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.
(© 2013 The American Laryngological, Rhinological and Otological Society, Inc.)
Databáze: MEDLINE
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