Predöhl, Friederike

[["dc.bibliographiccitation.firstpage","812"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Human Mutation"],["dc.bibliographiccitation.lastpage","819"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Sommen, Manou"],["dc.contributor.author","Schrauwen, Isabelle"],["dc.contributor.author","Vandeweyer, Geert"],["dc.contributor.author","Boeckx, Nele"],["dc.contributor.author","Corneveaux, Jason J."],["dc.contributor.author","van den Ende, Jenneke"],["dc.contributor.author","Boudewyns, An"],["dc.contributor.author","Leenheer, Els de"],["dc.contributor.author","Janssens, Sandra"],["dc.contributor.author","Claes, Kathleen"],["dc.contributor.author","Verstreken, Margriet"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Predoehl, Friederike"],["dc.contributor.author","Wuyts, Wim"],["dc.contributor.author","Mortier, Geert"],["dc.contributor.author","Bitner-Glindzicz, Maria"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Coucke, Paul"],["dc.contributor.author","Huentelman, Matthew J."],["dc.contributor.author","Camp, Guy van"],["dc.date.accessioned","2017-09-07T11:44:47Z"],["dc.date.available","2017-09-07T11:44:47Z"],["dc.date.issued","2016"],["dc.description.abstract","Although there are nearly 100 different causative genes identified for nonsyndromic hearing loss (NSHL), Sanger sequencing-based DNA diagnostics usually only analyses three, namely, GJB2, SLC26A4, and OTOF. As this is seen as inadequate, there is a need for high-throughput diagnostic methods to detect disease-causing variations, including single-nucleotide variations (SNVs), insertions/deletions (Indels), and copy-number variations (CNVs). In this study, a targeted resequencing panel for hearing loss was developed including 79 genes for NSHL and selected forms of syndromic hearing loss. One-hundred thirty one presumed autosomal-recessive NSHL (arNSHL) patients of Western-European ethnicity were analyzed for SNVs, Indels, and CNVs. In addition, we established a straightforward variant classification system to deal with the large number of variants encountered. We estimate that combining prescreening of GJB2 with our panel leads to a diagnosis in 25%-30% of patients. Our data show that after GJB2, the most commonly mutated genes in a Western-European population are TMC1, MYO15A, and MYO7A (3.1%). CNV analysis resulted in the identification of causative variants in two patients in OTOA and STRC. One of the major challenges for diagnostic gene panels is assigning pathogenicity for variants. A collaborative database collecting all identified variants from multiple centers could be a valuable resource for hearing loss diagnostics."],["dc.identifier.doi","10.1002/humu.22999"],["dc.identifier.gro","3141647"],["dc.identifier.isi","000379932300012"],["dc.identifier.pmid","27068579"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5010"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley-blackwell"],["dc.relation.eissn","1098-1004"],["dc.relation.issn","1059-7794"],["dc.title","DNA Diagnostics of Hereditary Hearing Loss: A Targeted Resequencing Approach Combined with a Mutation Classification System"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","E1717"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences of the United States of America"],["dc.bibliographiccitation.lastpage","E1726"],["dc.bibliographiccitation.volume","114"],["dc.contributor.author","Picher, Maria Magdalena"],["dc.contributor.author","Gehrt, Anna"],["dc.contributor.author","Meese, Sandra"],["dc.contributor.author","Ivanovic, Aleksandra"],["dc.contributor.author","Predoehl, Friederike"],["dc.contributor.author","Jung, SangYong"],["dc.contributor.author","Schrauwen, Isabelle"],["dc.contributor.author","Dragonetti, Alberto Giulio"],["dc.contributor.author","Colombo, Roberto"],["dc.contributor.author","Van Camp, Guy"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2018-01-17T11:41:34Z"],["dc.date.available","2018-01-17T11:41:34Z"],["dc.date.issued","2017-02-28"],["dc.description.abstract","Ca2+-binding protein 2 (CaBP2) inhibits the inactivation of heterologously expressed voltage-gated Ca2+ channels of type 1.3 (CaV1.3) and is defective in human autosomal-recessive deafness 93 (DFNB93). Here, we report a newly identified mutation in CABP2 that causes a moderate hearing impairment likely via nonsense-mediated decay of CABP2-mRNA. To study the mechanism of hearing impairment resulting from CABP2 loss of function, we disrupted Cabp2 in mice (Cabp2LacZ/LacZ ). CaBP2 was expressed by cochlear hair cells, preferentially in inner hair cells (IHCs), and was lacking from the postsynaptic spiral ganglion neurons (SGNs). Cabp2LacZ/LacZ mice displayed intact cochlear amplification but impaired auditory brainstem responses. Patch-clamp recordings from Cabp2LacZ/LacZ IHCs revealed enhanced Ca2+-channel inactivation. The voltage dependence of activation and the number of Ca2+ channels appeared normal in Cabp2LacZ/LacZ mice, as were ribbon synapse counts. Recordings from single SGNs showed reduced spontaneous and sound-evoked firing rates. We propose that CaBP2 inhibits CaV1.3 Ca2+-channel inactivation, and thus sustains the availability of CaV1.3 Ca2+ channels for synaptic sound encoding. Therefore, we conclude that human deafness DFNB93 is an auditory synaptopathy."],["dc.identifier.doi","10.1073/pnas.1617533114"],["dc.identifier.pmid","28183797"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11687"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1091-6490"],["dc.title","Ca2+-binding protein 2 inhibits Ca2+-channel inactivation in mouse inner hair cells"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","636"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","American journal of human genetics"],["dc.bibliographiccitation.lastpage","645"],["dc.bibliographiccitation.volume","91"],["dc.contributor.author","Schrauwen, Isabelle"],["dc.contributor.author","Helfmann, Sarah"],["dc.contributor.author","Inagaki, Akira"],["dc.contributor.author","Predoehl, Friederike"],["dc.contributor.author","Tabatabaiefar, Mohammad Amin"],["dc.contributor.author","Picher, Maria Magdalena"],["dc.contributor.author","Sommen, Manou"],["dc.contributor.author","Seco, Celia Zazo"],["dc.contributor.author","Oostrik, Jaap"],["dc.contributor.author","Kremer, Hannie"],["dc.contributor.author","Dheedene, A."],["dc.contributor.author","Claes, Charlotte"],["dc.contributor.author","Fransen, Erik"],["dc.contributor.author","Chaleshtori, Morteza Hashemzadeh"],["dc.contributor.author","Coucke, Paul"],["dc.contributor.author","Lee, Amy"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Camp, Guy van"],["dc.date.accessioned","2017-09-07T11:48:23Z"],["dc.date.available","2017-09-07T11:48:23Z"],["dc.date.issued","2012"],["dc.description.abstract","CaBPs are a family of Ca2+-binding proteins related to calmodulin and are localized in the brain and sensory organs, including the retina and cochlea. Although their physiological roles are not yet fully elucidated, CaBPs modulate Ca2+ signaling through effectors such as voltage-gated Ca-v Ca2+ channels. In this study, we identified a splice-site mutation (c.637+1G>T) in Ca2+-binding protein 2 (CABP2) in three consanguineous Iranian families affected by moderate-to-severe hearing loss. This mutation, most likely a founder mutation, probably leads to skipping of exon 6 and premature truncation of the protein (p.Phe164Serfs(star)4). Compared with wild-type CaBP2, the truncated CaBP2 showed altered Ca2+ binding in isothermal titration calorimetry and less potent regulation of Ca(v)1.3 Ca2+ channels. We show that genetic defects in CABP2 cause moderate-to-severe sensorineural hearing impairment. The mutation might cause a hypofunctional CaBP2 defective in Ca2+ sensing and effector regulation in the inner ear."],["dc.identifier.doi","10.1016/j.ajhg.2012.08.018"],["dc.identifier.gro","3142453"],["dc.identifier.isi","000309568500006"],["dc.identifier.pmid","22981119"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8452"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Cell Press"],["dc.relation.issn","0002-9297"],["dc.title","A Mutation in CABP2, Expressed in Cochlear Hair Cells, Causes Autosomal-Recessive Hearing Impairment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","995"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Otology & Neurotology"],["dc.bibliographiccitation.lastpage","1004"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Predoehl, Friederike"],["dc.contributor.author","Starr, Arnold"],["dc.date.accessioned","2017-09-07T11:53:12Z"],["dc.date.available","2017-09-07T11:53:12Z"],["dc.date.issued","2013"],["dc.identifier.doi","10.1097/mao.0b013e3182814d4a"],["dc.identifier.gro","3145056"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2750"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","1531-7129"],["dc.title","Review of Hair Cell Synapse Defects in Sensorineural Hearing Impairment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","651935"],["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Burfeind, Dinah"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Krinner, Stefanie"],["dc.contributor.author","Predoehl, Friederike"],["dc.contributor.author","Vogl, Christian"],["dc.date.accessioned","2021-04-29T08:36:41Z"],["dc.date.available","2021-04-29T08:36:41Z"],["dc.date.issued","2021"],["dc.description.abstract","The afferent synapses between inner hair cells (IHC) and spiral ganglion neurons are specialized to faithfully encode sound with sub-millisecond precision over prolonged periods of time. Here, we studied the role of Rab3 interacting molecule-binding proteins (RIM-BP) 1 and 2 - multidomain proteins of the active zone known to directly interact with RIMs, Bassoon and Ca V 1.3 - in IHC presynaptic function and hearing. Recordings of auditory brainstem responses and otoacoustic emissions revealed that genetic disruption of RIM-BPs 1 and 2 in mice (RIM-BP1/2-/- ) causes a synaptopathic hearing impairment exceeding that found in mice lacking RIM-BP2 (RIM-BP2-/- ). Patch-clamp recordings from RIM-BP1/2-/- IHCs indicated a subtle impairment of exocytosis from the readily releasable pool of synaptic vesicles that had not been observed in RIM-BP2-/- IHCs. In contrast, the reduction of Ca2+-influx and sustained exocytosis was similar to that in RIMBP2-/- IHCs. We conclude that both RIM-BPs are required for normal sound encoding at the IHC synapse, whereby RIM-BP2 seems to take the leading role."],["dc.identifier.doi","10.3389/fnmol.2021.651935"],["dc.identifier.pmid","33867935"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/84562"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/237"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/114"],["dc.language.iso","en"],["dc.notes.intern","DeepGreen Import"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | B05: Quantitative molekulare Physiologie aktiver Zonen in Calyx-Synapsen"],["dc.relation.eissn","1662-5099"],["dc.relation.issn","1662-5099"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","RIM-Binding Proteins Are Required for Normal Sound-Encoding at Afferent Inner Hair Cell Synapses"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","E3141"],["dc.bibliographiccitation.issue","24"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","E3149"],["dc.bibliographiccitation.volume","112"],["dc.contributor.author","Jung, Sangyong"],["dc.contributor.author","Oshima-Takago, Tomoko"],["dc.contributor.author","Chakrabarti, Rituparna"],["dc.contributor.author","Wong, Aaron B."],["dc.contributor.author","Jing, Zhizi"],["dc.contributor.author","Yamanbaeva, Gulnara"],["dc.contributor.author","Picher, Maria Magdalena"],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Göttfert, Fabian"],["dc.contributor.author","Predoehl, Friederike"],["dc.contributor.author","Michel, Katrin"],["dc.contributor.author","Hell, Stefan"],["dc.contributor.author","Schoch, Susanne"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Wichmann, Carolin"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:43:46Z"],["dc.date.available","2017-09-07T11:43:46Z"],["dc.date.issued","2015"],["dc.description.abstract","Ca2+ influx triggers the fusion of synaptic vesicles at the presynaptic active zone (AZ). Here we demonstrate a role of Ras-related in brain 3 (Rab3)-interacting molecules 2 alpha and beta (RIM2 alpha and RIM2 beta) in clustering voltage-gated Ca(V)1.3 Ca2+ channels at the AZs of sensory inner hair cells (IHCs). We show that IHCs of hearing mice express mainly RIM2 alpha, but also RIM2 beta and RIM3., which all localize to the AZs, as shown by immunofluorescence microscopy. Immunohistochemistry, patch-clamp, fluctuation analysis, and confocal Ca2+ imaging demonstrate that AZs of RIM2 alpha-deficient IHCs cluster fewer synaptic Ca(V)1.3 Ca2+ channels, resulting in reduced synaptic Ca2+ influx. Using superresolution microscopy, we found that Ca2+ channels remained clustered in stripes underneath anchored ribbons. Electron tomography of high-pressure frozen synapses revealed a reduced fraction of membrane-tethered vesicles, whereas the total number of membrane-proximal vesicles was unaltered. Membrane capacitance measurements revealed a reduction of exocytosis largely in proportion with the Ca2+ current, whereas the apparent Ca2+ dependence of exocytosis was unchanged. Hair cell-specific deletion of all RIM2 isoforms caused a stronger reduction of Ca2+ influx and exocytosis and significantly impaired the encoding of sound onset in the postsynaptic spiral ganglion neurons. Auditory brainstem responses indicated a mild hearing impairment on hair cell-specific deletion of all RIM2 isoforms or global inactivation of RIM2 alpha. We conclude that RIM2 alpha and RIM2 beta promote a large complement of synaptic Ca2+ channels at IHC AZs and are required for normal hearing."],["dc.identifier.doi","10.1073/pnas.1417207112"],["dc.identifier.gro","3141887"],["dc.identifier.isi","000356251800010"],["dc.identifier.pmid","26034270"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2178"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0027-8424"],["dc.title","Rab3-interacting molecules 2α and 2β promote the abundance of voltage-gated CaV1.3 Ca2+ channels at hair cell active zones"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]