TY - JOUR
T1 - Congenital hearing impairment associated with peripheral cochlear nerve dysmyelination in glycosylation-deficient muscular dystrophy
AU - Morioka, Shigefumi
AU - Sakaguchi, Hirofumi
AU - Mohri, Hiroaki
AU - Taniguchi-Ikeda, Mariko
AU - Kanagawa, Motoi
AU - Suzuki, Toshiaki
AU - Miyagoe-Suzuki, Yuko
AU - Toda, Tatsushi
AU - Saito, Naoaki
AU - Ueyama, Takehiko
N1 - Funding Information:
This work was supported by JSPS KAKENHI (#17H04042 and #19K22472 to TU, and #18K09383 to HS), the AMED (JP19ek0109398 to TU), the Uehara Foundation (# 201320273 to TU), the Hyogo Science and Technology Association (#30075 to TU), the Naito Foundation (to TU), and the joint research program of the Biosignal Research Center, Kobe University (#281005, #291004 and #301004 to HS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Rion Co. Ltd., Tokyo, Japan for free offer to use the Integrity 500 System, which can measure ABR in awake patients. We also thank Ms Mai Kondo, Division of Molecular Brain Science, Kobe University Graduate School of Medicine, for the technical assistance.
Publisher Copyright:
© 2020 Morioka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2020/5
Y1 - 2020/5
N2 - Hearing loss (HL) is one of the most common sensory impairments and etiologically and genetically heterogeneous disorders in humans. Muscular dystrophies (MDs) are neuromuscular disorders characterized by progressive degeneration of skeletal muscle accompanied by non-muscular symptoms. Aberrant glycosylation of α-dystroglycan causes at least eighteen subtypes of MD, now categorized as MD-dystroglycanopathy (MD-DG), with a wide spectrum of non-muscular symptoms. Despite a growing number of MD-DG subtypes and increasing evidence regarding their molecular pathogeneses, no comprehensive study has investigated sensorineural HL (SNHL) in MD-DG. Here, we found that two mouse models of MD-DG, Largemyd/myd and POMGnT1-KO mice, exhibited congenital, non-progressive, and mild-to-moderate SNHL in auditory brainstem response (ABR) accompanied by extended latency of wave I. Profoundly abnormal myelination was found at the peripheral segment of the cochlear nerve, which is rich in the glycosylated α-dystroglycan–laminin complex and demarcated by “the glial dome.” In addition, patients with Fukuyama congenital MD, a type of MD-DG, also had latent SNHL with extended latency of wave I in ABR. Collectively, these findings indicate that hearing impairment associated with impaired Schwann cell-mediated myelination at the peripheral segment of the cochlear nerve is a notable symptom of MD-DG.
AB - Hearing loss (HL) is one of the most common sensory impairments and etiologically and genetically heterogeneous disorders in humans. Muscular dystrophies (MDs) are neuromuscular disorders characterized by progressive degeneration of skeletal muscle accompanied by non-muscular symptoms. Aberrant glycosylation of α-dystroglycan causes at least eighteen subtypes of MD, now categorized as MD-dystroglycanopathy (MD-DG), with a wide spectrum of non-muscular symptoms. Despite a growing number of MD-DG subtypes and increasing evidence regarding their molecular pathogeneses, no comprehensive study has investigated sensorineural HL (SNHL) in MD-DG. Here, we found that two mouse models of MD-DG, Largemyd/myd and POMGnT1-KO mice, exhibited congenital, non-progressive, and mild-to-moderate SNHL in auditory brainstem response (ABR) accompanied by extended latency of wave I. Profoundly abnormal myelination was found at the peripheral segment of the cochlear nerve, which is rich in the glycosylated α-dystroglycan–laminin complex and demarcated by “the glial dome.” In addition, patients with Fukuyama congenital MD, a type of MD-DG, also had latent SNHL with extended latency of wave I in ABR. Collectively, these findings indicate that hearing impairment associated with impaired Schwann cell-mediated myelination at the peripheral segment of the cochlear nerve is a notable symptom of MD-DG.
UR - http://www.scopus.com/inward/record.url?scp=85086052642&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85086052642&partnerID=8YFLogxK
U2 - 10.1371/journal.pgen.1008826
DO - 10.1371/journal.pgen.1008826
M3 - Article
C2 - 32453729
AN - SCOPUS:85086052642
VL - 16
JO - PLoS Genetics
JF - PLoS Genetics
SN - 1553-7390
IS - 5
M1 - e1008826
ER -