USH2 Caused by <i>GPR98</i> Mutation Diagnosed by Massively Parallel Sequencing in Advance of the Occurrence of Visual Symptoms

Moteki, Hideaki; Yoshimura, Hidekane; Azaiez, Héla; Booth, Kevin T.; Shearer, A. Eliot; Sloan, Christina M.; Kolbe, Diana L.; Murata, Toshinori; Smith, Richard J.H.; Usami, Shin‐ichi

doi:10.1177/0003489415574070

Cited by 9 publications

(9 citation statements)

References 22 publications

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“…The initial diagnosis of all mentioned patients did not include retinal defects as in other USH2C patients. In case of family B48, it is likely that the patients of our families (8 and 10 years old) were too young at the time of their initial examination, since visual symptoms usually manifest only in the second decade 55 . In contrast, the members of family A10 were clearly above the manifestation age and had no retinal defects.…”

Section: Discussionmentioning

confidence: 91%

Comprehensive molecular analysis of 61 Egyptian families with hereditary nonsyndromic hearing loss

et al. 2020

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Nonsyndromic hearing loss is an extremely heterogeneous disorder. Thus, clinical diagnostics is challenging, in particular due to differences in the etiology of hearing loss between populations. With this study, we wanted to elucidate the genetic basis of hearing loss in 61 consanguineous Egyptian families. In 25 families, linkage analysis was used as a prescreening to identify regions for targeted sequencing of candidate genes. Initially, the coding regions of 12 and later of 94 genes associated with hearing loss were enriched and subjected to massively parallel sequencing (MPS) with diagnostic yields of 36% and 75%, respectively. Causative variants were identified in 48 families (79%). They were found in 23 different genes with the majority being located in MYO15A (15.3%), SLC26A4 (9.7%), GJB2 (8.3%), and MYO7A (6.4%). As many as 32 variants were novel ones at the time of detection. Five variants were shared by two, three, or even four families. Our study provides a first survey of the mutational spectrum of deaf patients in Egypt revealing less GJB2 variants than in many European populations. It underlines the value of targeted enrichment of well‐selected deafness genes in combination with MPS in the diagnostics of this frequent and genetically heterogeneous disorder.

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Section: Discussionmentioning

confidence: 91%

Comprehensive molecular analysis of 61 Egyptian families with hereditary nonsyndromic hearing loss

et al. 2020

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“…Several adhesion GPRs have been shown to be important for cochlear development. First, mutation of Gpr98 causes moderate to severe congenital hearing loss in humans ( Moteki et al, 2015 ; Bousfiha et al, 2017 ). In mice, Gpr98 (or Very Large G-protein coupled receptor 1, Vlgr1) is required for the assembly of the ankle link complex and in the subsequent bundle development and survival of cochlear hair cells ( McGee et al, 2006 ; Zou et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Gpr125 Marks Distinct Cochlear Cell Types and Is Dispensable for Cochlear Development and Hearing

Sun

Atkinson

Billings

et al. 2021

Front. Cell Dev. Biol.

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The G protein-coupled receptor (GPR) family critically regulates development and homeostasis of multiple organs. As a member of the GPR adhesion family, Gpr125 (Adgra3) modulates Wnt/PCP signaling and convergent extension in developing zebrafish, but whether it is essential for cochlear development in mammals is unknown. Here, we examined the Gpr125lacZ/+ knock-in mice and show that Gpr125 is dynamically expressed in the developing and mature cochleae. From embryonic day (E) 15.5 to postnatal day (P) 30, Gpr125-β-Gal is consistently expressed in the lesser epithelial ridge and its presumed progenies, the supporting cell subtypes Claudius cells and Hensen’s cells. In contrast, Gpr125-β-Gal is expressed transiently in outer hair cells, epithelial cells in the lateral cochlear wall, interdental cells, and spiral ganglion neurons in the late embryonic and early postnatal cochlea. In situ hybridization for Gpr125 mRNA confirmed Gpr125 expression and validated loss of expression in Gpr125lacZ/lacZ cochleae. Lastly, Gpr125lacZ/+ and Gpr125lacZ/lacZ cochleae displayed no detectable loss or disorganization of either sensory or non-sensory cells in the embryonic and postnatal ages and exhibited normal auditory physiology. Together, our study reveals that Gpr125 is dynamically expressed in multiple cell types in the developing and mature cochlea and is dispensable for cochlear development and hearing.

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“…Another aGPCR, VLGR1 (also referred to by ADGRV1, GPR98, MASS1), was first linked to audiogenic seizures in a mouse model and has been found to be linked to Usher syndrome, an autosomal recessive disorder characterized by hearing loss, retinitis pigmentosa, and vestibular dysfunction (Weston et al, ; Hilgert, ; Moteki et al, ; Yang et al, ). Expressed on mature OLs, VLGR1 is also associated with expression of myelin‐associated glycoprotein (MAG) (Shin et al, ), a cell membrane glycoprotein identified as an inhibitor of axon growth in the CNS after injury (McKerracher et al, ; DeBellard et al, ; Li et al, ).…”

Section: Introductionmentioning

confidence: 99%

Adhesion G‐protein coupled receptors and extracellular matrix proteins: Roles in myelination and glial cell development

Mehta

Piao

2017

Developmental Dynamics

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Background Adhesion G protein-coupled receptors (aGPCRs) are a large family of transmembrane proteins that play important roles in many processes during development, primarily through cell-cell and cell-extracellular matrix (ECM) interactions. In the nervous system, they have been linked to the complex process of myelination, both in the central and peripheral nervous system. Results GPR126 is essential in Schwann cell-mediated myelination in the peripheral nervous system (PNS), while GPR56 is involved in oligodendrocyte development central nervous system (CNS) myelination. VLGR1 is another aGPCR that is associated with the expression of myelin-associated glycoprotein (MAG) which has inhibitory effects on the process of nerve repair. The ECM is composed of a vast array of structural proteins, three of which interact specifically with aGPCRs: collagen III/GPR56, collagen IV/GPR126, and laminin-211/GPR126. Conclusions As druggable targets, aGPCRs are valuable in their ability to unlock treatment for a wide variety of currently debilitating myelin disorders.

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USH2 Caused by GPR98 Mutation Diagnosed by Massively Parallel Sequencing in Advance of the Occurrence of Visual Symptoms

Cited by 9 publications

References 22 publications

Comprehensive molecular analysis of 61 Egyptian families with hereditary nonsyndromic hearing loss

Comprehensive molecular analysis of 61 Egyptian families with hereditary nonsyndromic hearing loss

Gpr125 Marks Distinct Cochlear Cell Types and Is Dispensable for Cochlear Development and Hearing

Adhesion G‐protein coupled receptors and extracellular matrix proteins: Roles in myelination and glial cell development

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