Christine Petit

Christine Petit
Institut Pasteur and Collège de France, Paris

MD, PhD

About

487
Publications
57,568
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30,370
Citations
Citations since 2016
95 Research Items
8666 Citations
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201620172018201920202021202202004006008001,0001,2001,400
201620172018201920202021202202004006008001,0001,2001,400
201620172018201920202021202202004006008001,0001,2001,400

Publications

Publications (487)
Article
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Hearing depends on fast and sustained calcium-dependent synaptic vesicle fusion at the ribbon synapses of cochlear inner hair cells (IHCs). The implication of the canonical neuronal SNARE complex in this exocytotic process has remained so far controversial. We investigated the role of SNAP-25, a key component of this complex, in hearing, by generat...
Chapter
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Among the senses, the mechanical ones, hearing, balance, touch, and proprioception, are most numerous but least understood. The status of hearing is very specific. This sense is deeply rooted in social living that requires effective means of communication. In many species, communication is ensured by sounds. Animals produce a large variety of sound...
Article
Auditory Brainstem Responses (ABRs) are a reliably robust measure of auditory thresholds in the mammalian hearing system and can be used to determine deficits in the auditory periphery. However, because these measures are limited to the lower stages of the auditory pathway, they are insensitive to changes or deficits that occur in the thalamic and...
Article
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Background Deafness is the most prevalent human sensorineural defect. It may occur as a result of an external auditory canal involvement, or a deficiency in the sound conduction mechanism, or an impairment of the cochlea, the cochlear nerve or central auditory perception. The genetic causes are the most common, as approximately 70% of hearing disor...
Article
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Since the 1990s, the study of inherited hearing disorders, mostly those detected at birth, in the prelingual period or in young adults, has led to the identification of their causal genes. The genes responsible for more than 140 isolated (non-syndromic) and about 400 syndromic forms of deafness have already been discovered. Studies of mouse models...
Article
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Purpose: Biallelic variants in CLRN1 are responsible for Usher syndrome 3A and non-syndromic rod-cone dystrophy (RCD). Retinal findings in Usher syndrome 3A have not been well defined. We report the detailed phenotypic description of RCD associated with CLRN1 variants in a prospective cohort. Methods: Patients were clinically investigated at the...
Article
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Alpha-Mannosidosis (AM) is an ultra-rare storage disorder caused by a deficiency of lysosomal alpha-mannosidase encoded by the MAN2B1 gene. Clinical presentation of AM includes mental retardation, recurrent infections, hearing loss, dysmorphic features, and motor dysfunctions. AM has never been reported in Tunisia. We report here the clinical and g...
Article
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In contrast to USH2A, variants in ADGRV1 are a minor cause of Usher syndrome type 2, and the associated phenotype is less known. The purpose of the study was to characterize the retinal phenotype of 18 ADGRV1 patients (9 male, 9 female; median age 52 years) and compare it with that of 204 USH2A patients (111 male, 93 female; median age 43 years) in...
Preprint
Full-text available
Deafness has a very variable disease. It may occur as a result of external auditory canal involvement or a deficiency in the sound conduction mechanism (transmission deafness) or impairment of the cochlear, cochlear nerve or central auditory perception. Genetics is the most common cause, as approximately 70% of hearing disorders are of hereditary o...
Article
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Background Harmonin Homogy Domains (HHD) are recently identified orphan domains of about 70 residues folded in a compact five alpha-helix bundle that proved to be versatile in terms of function, allowing for direct binding to a partner as well as regulating the affinity and specificity of adjacent domains for their own targets. Adding their small s...
Article
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The decline of speech intelligibility in presbycusis can be regarded as resulting from the combined contribution of two main groups of factors: (1) audibility-related factors and (2) age-related factors. In particular, there is now an abundant scientific literature on the crucial role of suprathreshold auditory abilities and cognitive functions, wh...
Article
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Nematostella , petite anémone de mer, possède de fascinantes propriétés, telles que la régénération du corps entier, l’absence de signes de vieillissement et d’affections liées à l’âge comme, par exemple, le développement de cancers. Elle se cultive aisément et se reproduit en laboratoire. Malgré son aspect « simple », cet invertébré marin de l’emb...
Article
Introduction: Auditory neuropathy is a hearing disorder where outer hair cell function within the cochlea is normal, but inner hair cell and/or the auditory nerve function is disrupted. It is a heterogeneous disorder, which can have either congenital or acquired causes. Methods: We found a disease-segregating mutation in the X-linked AIFM1 gene...
Article
Adhesion glycoproteins are implicated in the pathophysiology of hearing loss, the most frequent inherited sensory disorder, affecting 1 in 1000 new-borns. Exome sequencing of a consanguineous Moroccan patient with mild hearing loss identified for the first time in a North African family a single homozygous mutation c.72delA in MPZL2 gene, encoding...
Article
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According to a novel hypothesis (Arnal et al., 2015, Current Biology 25:2051-2056), auditory roughness, or temporal envelope modulations between 30 and 150 Hz, are present in both natural and artificial human alarm signals, which boosts the detection of these alarms in various tasks. These results also shed new light on the unpleasantness of disson...
Article
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The hair bundle of cochlear hair cells is the site of auditory mechanoelectrical transduction. It is formed by three rows of stiff microvilli-like protrusions of graduated heights, the short, middle-sized, and tall stereocilia. In developing and mature sensory hair cells, stereocilia are connected to each other by various types of fibrous links. Tw...
Article
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Calcium is a second messenger crucial to a myriad of cellular processes ranging from regulation of metabolism and cell survival to vesicle release and motility. Current strategies to directly manipulate endogenous calcium signals lack cellular and subcellular specificity. We introduce SpiCee, a versatile and genetically encoded chelator combining l...
Article
Background: Pathogenic variants of USH1C, encoding a PDZ-domain-containing protein called harmonin, have been known to cause autosomal recessive syndromic or nonsyndromic hearing loss (NSHL). We identified a causative gene in a large Korean family with NSHL showing a typical pattern of autosomal dominant (AD) inheritance. Methods: Exome sequenci...
Article
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Purpose: to determine a detailed clinical and haplotypic variability of the Slovenian USH2A patients with homozygous c.11864G>A (p.Trp3955Ter) nonsense mutation and to develop sensitive, accurate and rapid screening test. Methods: Ten unrelated homozygous patients with detailed ophthalmological exam were included in our study. The High-Resolutio...
Article
Mutations in the mesenchymal epithelial transition factor (MET) gene are frequently associated with multiple human cancers but can also lead to human non-syndromic autosomal recessive deafness (DFNB97). In the present study, we identified a novel homozygous missense mutation in the METgene causing a non-syndromic hearing impairment DFNB97 form. Who...
Article
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Significance Patients lacking either otogelin or otogelin-like have congenital mild-to-moderate hearing impairment similar to that in patients lacking stereocilin. Stereocilin is associated with 2 types of links specific to the mechanosensitive antenna (stereocilia bundle) of cochlear outer hair cells: The horizontal top connectors joining stereoci...
Article
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USH2A mutation is the most common cause of retinitis pigmentosa, with or without hearing impairment. Patients most commonly exhibit hyperautofluorescent ring on fundus autofluorescence imaging (FAF) and rod-cone dystrophy on electrophysiology. A detailed study of three USH2A patients with a rare pattern of double hyperautofluorescent rings was perf...
Article
Hereditary distal renal tubular acidosis (dRTA) is a rare disorder characterized by metabolic acidosis due to impaired renal acid excretion. To date, three genes (ATP6V1B1, ATP6V0A4 and SLC4A1) have been reported to be responsible for this genetic disorder. Notably, mutations of ATP6V1B1 gene, which encode B1-subunit of H + -ATPase pump cause dista...
Article
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Purpose Usher syndrome (USH) is a multisensory deficiency involving vision, hearing and the vestibular system. The purpose of this study is to report on the functional data (i.e. electroretinography, visual fields, visual acuity) of patients with retinitis pigmentosa (RP) due to Usher syndrome that were collected in a multicentre European study (TR...
Article
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Background Co-occurrence of two genetic diseases is challenging for accurate diagnosis and genetic counseling. The recent availability of whole exome sequencing (WES) has dramatically improved the molecular diagnosis of rare genetic diseases in particular in consanguineous populations. Methods We report here on a consanguineous family from Southern...
Article
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Hearing relies on mechanically gated ion channels present in the actin-rich stereocilia bundles at the apical surface of cochlear hair cells. Our knowledge of the mechanisms underlying the formation and maintenance of the sound-receptive structure is limited. Utilizing a large-scale forward genetic screen in mice, genome mapping and gene complement...
Article
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Using adequate DNA barcodes is essential to unambiguously identify each DNA library within a multiplexed set of libraries sequenced using next-generation sequencers. We introduce DNABarcodeCompatibility, an R-package that allows one to design single or dual-barcoding multiplex experiments by imposing desired constraints on the barcodes (including s...
Article
Purpose: To document the rod-cone dystrophy phenotype of patients with Usher syndrome type 1 (USH1) harboring MYO7A mutations. Methods: Retrospective cohort study of 53 patients (42 families) with biallelic MYO7A mutations who underwent comprehensive examination, including functional visual tests and multimodal retinal imaging. Genetic analysis...
Article
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Purpose: Intraocular pressure leading to glaucoma is a major cause of childhood blindness in developing countries. In this study, we sought to identify gene variants potentially associated with primary congenital glaucoma (PCG) in the Mauritanian population. Methods: Using next-generation sequencing (NGS), a panel of PCG candidate genes was scre...
Article
The genetic approach, based on the study of inherited forms of deafness, has proven to be particularly effective for deciphering the molecular mechanisms underlying the development of the peripheral auditory system, the cochlea and its afferent auditory neurons, and how this system extracts the physical parameters of sound. Although this genetic di...
Article
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To describe retinal alterations detected by swept-source optical coherence tomography (SS-OCT) in paediatric patients with Usher syndrome type 1 (USH1) and to compare these findings to previously published reports. Thirty-two eyes from 16 patients (11 males and 5 females) with a genetic diagnosis of USH1 because of MYO7A mutations underwent SS-OCT....
Article
Full-text available
cGMP is critical to a variety of cellular processes, but the available tools to interfere with endogenous cGMP lack cellular and subcellular specificity. We introduce SponGee, a genetically encoded chelator of this cyclic nucleotide that enables in vitro and in vivo manipulations in single cells and in biochemically defined subcellular compartments...
Article
Significance Noise-induced hearing loss is a highly prevalent form of sensorineural hearing impairment affecting individuals of all ages. Noise exposure triggers a rapid increase in reactive oxygen species (ROS) levels, causing oxidative damage to auditory hair cells and resulting in hearing loss. Here we describe a novel mechanism of protection ag...
Article
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Transmitter release at auditory inner hair cell (IHC) ribbon synapses involves exocytosis of glutamatergic vesicles during voltage activation of L-type Cav1.3 calcium channels. At these synapses, the fast and indefatigable release of synaptic vesicles by IHCs is controlled by otoferlin, a six-C2-domain (C2-ABCDEF) protein that functions as a high-a...
Article
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Significance In humans, inner ear development is completed in utero, with hearing onset at ∼20 weeks of gestation. However, genetic forms of congenital deafness are typically diagnosed during the neonatal period. Gene therapy approaches in animal models should therefore be tested after the period of hearing onset, to determine whether they can reve...
Article
Full-text available
Using adequate DNA barcodes is essential to unambiguously identify each DNA library within a multiplexed set of libraries sequenced using next-generation sequencers. We introduce DNABarcodeCompatibility, an R-package that allows one to design single or dual-barcoding multiplex experiments by imposing desired constraints on the barcodes (including s...
Article
Up to five distinct cell-surface specializations interconnect the stereocilia and the kinocilium of the mature hair bundle in some species: kinocilial links, tip links, top connectors, shaft connectors, and ankle links. In developing hair bundles, transient lateral links are prominent. Mutations in genes encoding proteins associated with these link...
Article
Objective of the study:: Inborn lens opacity is the most frequent cause of childhood blindness. In this study, we aimed to define the presumed genetic cause of a congenital cataract present in a Mauritanian family over the last nine generations. Methods:: A family history of the disease and eye examination were carried out for the family members...
Article
Full-text available
In the adult auditory organ, mechanoelectrical transducer (MET) channels are essential for transducing acoustic stimuli into electrical signals. In the absence of incoming sound, a fraction of the MET channels on top of the sensory hair cells are open, resulting in a sustained depolarizing current. By genetically manipulating the in vivo expression...
Article
Purpose The aim of this study is to report on the results of color vision testing in a European cohort of patients with Usher syndrome (USH). We describe the results in relation to Usher type (USH1, USH2), age and visual acuity. Methods and Methods The color vision of 220 genetically confirmed adult USH patients, aged 18–70 years, was analyzed with...
Article
Full-text available
Clarin-1, a tetraspan-like membrane protein defective in Usher syndrome type IIIA (USH3A), is essential for hair bundle morphogenesis in auditory hair cells. We report a new synaptic role for clarin-1 in mouse auditory hair cells elucidated by characterization of Clrn1 total (Clrn1ex4-/-) and postnatal hair cell-specific conditional (Clrn1ex4fl/fl...
Article
Background: Consanguinity rate is high in Algeria, and the population is thus at high risk for genetic diseases transmitted on an autosomal recessive mode. Inherited congenital hearing impairment (HI) is a highly heterogeneous disorder, which affects approximately 1 in 800 Algerian newborns. Several hundreds of genes responsible for deafness have...
Article
Deafness and myopia syndrome is characterized by moderate-profound, bilateral, congenital or prelingual deafness and high myopia. Autosomal recessive non-syndromic hearing loss is one of the most prevalent human genetic sensorineural defects. Myopia is by far the most common human eye disorder that is known to have a clear heritable component. The...
Article
Full-text available
Usher syndrome type 1 (USH1) is a major cause of inherited deafness and blindness in humans. The eye disorder is often referred to as retinitis pigmentosa, which is characterized by a secondary cone degeneration following the rod loss. The development of treatments to prevent retinal degeneration has been hampered by the lack of clear evidence for...
Article
Context: Presbycusis, an age-related hearing impairment (ARHI), represents the most common sensory disability in adults. Today, the molecular mechanisms underlying presbycusis remain unclear. This is in particular due to the fact that ARHI is a multifactorial complex disorder resulting from several genomic factors interacting with lifelong cumulati...
Article
Full-text available
Hearing relies on rapid, temporally precise, and sustained neurotransmitter release at the ribbon synapses of sensory cells, the inner hair cells (IHCs). This process requires otoferlin, a six C2-domain, Ca2+-binding transmembrane protein of synaptic vesicles. To decipher the role of otoferlin in the synaptic vesicle cycle, we produced knock-in mic...