Dr Mirna Mustapha
School of Biosciences
Senior Research Fellow
+44 114 222 1082
Full contact details
School of Biosciences
B1 224
Alfred Denny Building
Western Bank
Sheffield
S10 2TN
- Research interests
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Our lab is interested in understanding the cellular and molecular mechanisms underlying peripheral auditory neuropathy. We utilize transgenic mouse models and a variety of cutting edge molecular, microscopic, and physiological approaches to understand cochlear neurogenesis, and neuropathy associated with congenital and age-related hearing impairment.
Blindness cuts us off from things, but deafness cuts us off from people
Helen Keller
Author
Deafness is a common health problem
Hearing impairment is the most frequently occurring sensorineural defect in humans. The sense of hearing originates in the cochlea, a structure in the inner ear. Information about timing, frequency, and intensity of sounds is transmitted from the hair cells in the cochlea to the brain via spiral ganglion neurons by converting sound waves into nerve impulses.
Any disruptions in this sensory pathway could result in auditory neuropathy and hearing impairment.
Causes
Auditory neuropathy is a type of hearing impairment caused by a defect in the hair cells and/or their synapses (synaptopathy) or the spiral ganglion neurons (neuropathy). It can affect people of all ages, from birth (congenital) through adulthood (acquired or age-related).
Genetically inherited auditory neuropathy can be either isolated or associated with a systemic neurodegenerative disorder such as Charcot-Marie-Tooth disease or Friedreich’s ataxia.
Diagnosis
Auditory neuropathy can be diagnosed using hearing tests such as auditory brainstem response (ABR) and otoacoustic emissions (OAE). Auditory neuropathy is defined by an abnormal ABR reading together with a normal OAE reading.
An abnormal ABR reading can be the result of damage to the auditory nerve pathway, including the inner hair cells, their connection to the nerve (synapses), and/or the nerve itself (spiral ganglion neurons).
Why we care
Cochlear implants are currently the standard of care for hearing impairment. However, cochlear implant performance relies on healthy spiral ganglion neurons. Therefore, knowledge of the exact site of dysfunction (i.e., whether the patient suffers from synaptopathy or neuropathy) would aid in assessing the benefit of this treatment for patients.
There are currently no available clinical tests that can distinguish between cochlear synaptopathy and neuropathy, but molecular genetic diagnosis can.
Our long-term goal is to identify genes that are involved in congenital and age-related cochlear synaptopathy and/or neuropathy. Identification of these genes will improve the clinical diagnosis and our understanding of the molecular mechanisms that regulate the innervation of the cochlea and that cause cochlear neuropathy.
- Publications
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Show: Featured publications All publications
Featured publications
Journal articles
- Single-cell RNA analysis of type I spiral ganglion neurons reveals a Lmx1a population in the cochlea. Frontiers in Molecular Neuroscience, 13. View this article in WRRO
- TSP1 and TSP2 Have Unique and Overlapping Roles in Protecting against Noise-Induced Auditory Synaptopathy. Neuroscience, 408, 68-80.
All publications
Journal articles
- 19 POLD3 deficiency is associated with syndromic severe combined immunodeficiency including neurodevelopmental delay and hearing impairment. Clinical Immunology, 262, 109961-109961.
- POLD3 deficiency is associated with severe combined immunodeficiency, neurodevelopmental delay, and hearing impairment. Clinica Chimica Acta, 558, 118291-118291.
- BAI1 localizes AMPA receptors at the cochlear afferent post-synaptic density and is essential for hearing. Cell Reports, 43(4), 114025-114025.
- POLD3 deficiency is associated with severe combined immunodeficiency, neurodevelopmental delay, and hearing impairment. Clinical Immunology, 251, 109326-109326.
- Corrigendum: Single-Cell RNA Analysis of Type I Spiral Ganglion Neurons Reveals a Lmx1a Population in the Cochlea.. Front Mol Neurosci, 14, 686790.
- Age‐related changes in the biophysical and morphological characteristics of mouse cochlear outer hair cells. The Journal of Physiology. View this article in WRRO
- Single-cell RNA analysis of type I spiral ganglion neurons reveals a Lmx1a population in the cochlea. Frontiers in Molecular Neuroscience, 13. View this article in WRRO
- TSP1 and TSP2 Have Unique and Overlapping Roles in Protecting against Noise-Induced Auditory Synaptopathy. Neuroscience, 408, 68-80.
- Pathogenic Variants in GPC4 Cause Keipert Syndrome. The American Journal of Human Genetics, 104(5), 914-924.
- Hair Cell Afferent Synapses: Function and Dysfunction. Cold Spring Harbor Perspectives in Medicine, 9(12), a033175-a033175.
- Myosin-X knockout is semi-lethal and demonstrates that myosin-X functions in neural tube closure, pigmentation, hyaloid vasculature regression, and filopodia formation. Scientific Reports, 7(1).
- Contribution of beta1- and beta2-adrenergic receptors to cochlear function. Medical research archives, 5(9). View this article in WRRO
- Thyroid hormone is required for the pruning of afferent type II spiral ganglion neurons in the mouse cochlea. Neuroscience, 312, 165-178.
- Facial Nerve Recovery in KbDb and C1q Knockout Mice. Plastic and Reconstructive Surgery - Global Open, 4(12), e1186-e1186.
- Thyroid hormone is required for pruning, functioning and long-term maintenance of afferent inner hair cell synapses. European Journal of Neuroscience, 43(2), 148-161.
- Increased sensitivity to kindling in mice lacking TSP1. Neuroscience, 305, 302-308.
- Thrombospondins 1 and 2 are important for afferent synapse formation and function in the inner ear. European Journal of Neuroscience, 39(8), 1256-1267.
- Genetic Background of Prop1 df Mutants Provides Remarkable Protection Against Hypothyroidism-Induced Hearing Impairment. Journal of the Association for Research in Otolaryngology, 13(2), 173-184.
- High Frequency of the p.R34X Mutation in the TMC1 Gene Associated with Nonsyndromic Hearing Loss Is Due to Founder Effects. Genetic Testing and Molecular Biomarkers, 14(3), 307-311.
- Deafness and Permanently Reduced Potassium Channel Gene Expression and Function in Hypothyroid Pit1dw Mutants. Journal of Neuroscience, 29(4), 1212-1223.
- Hypothyroidism-induced deafness: Defects in neuronal development and sensory cell function. Developmental Biology, 319(2), 466-467.
- Whirler Mutant Hair Cells Have Less Severe Pathology than Shaker 2 or Double Mutants. Journal of the Association for Research in Otolaryngology, 8(3), 329-337.
- Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and families with DFNB31. Nature Genetics, 34(4), 421-428.
- Usher syndrome type I G (USH1G) is caused by mutations in the gene encoding SANS, a protein that associates with the USH1C protein, harmonin. Human Molecular Genetics, 12(5), 463-471.
- Otoancorin, an inner ear protein restricted to the interface between the apical surface of sensory epithelia and their overlying acellular gels, is defective in autosomal recessive deafness DFNB22. Proceedings of the National Academy of Sciences, 99(9), 6240-6245.
- A novel locus for Usher syndrome type I, USH1G, maps to chromosome 17q24–25. Human Genetics, 110(4), 348-350.
- DFNB31, a recessive form of sensorineural hearing loss, maps to chromosome 9q32-34. European Journal of Human Genetics, 10(3), 210-212.
- Non-syndromic recessive deafness in Jordan: mapping of a new locus to chromosome 9q34.3 and prevalence of DFNB1 mutations. European Journal of Human Genetics, 10(6), 391-394.
- DFNB21, 153-155.
- Autosomal recessive non-syndromic hearing loss in the Lebanese population: prevalence of the 30delG mutation and report of two novel mutations in the connexin 26 (GJB2) gene. Journal of Medical Genetics, 38(10), 36e-36.
- A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness. Nature Genetics, 21(4), 363-369.
- An alpha-tectorin gene defect causes a newly identified autosomal recessive form of sensorineural pre-lingual non-syndromic deafness, DFNB21. Human Molecular Genetics, 8(3), 409-412.
- The Usher syndrome in the Lebanese population and further refinement of the USH2A candidate region. Human Genetics, 103(2), 193-198.
- Identification of a locus on chromosome 7q31, DFNB14, responsible for prelingual sensorineural non-syndromic deafness. European Journal of Human Genetics, 6(6), 548-551.
- Further refinement of Pendred syndrome locus by homozygosity analysis to a 0.8 cM interval flanked by D7S496 and D7S2425.. Journal of Medical Genetics, 35(3), 202-204.
- A sensorineural progressive autosomal recessive form of isolated deafness, DFNB13, maps to chromosome 7q34-q36. European Journal of Human Genetics, 6(3), 245-250.
- Prelingual Deafness: High Prevalence of a 30delG Mutation in the Connexin 26 Gene. Human Molecular Genetics, 6(12), 2173-2177.
- POLD3 haploinsufficiency is linked to non-syndromic sensorineural adult-onset progressive hearing and balance impairments. European Journal of Human Genetics.
- The upregulation of K+ and HCN channels in developing spiral ganglion neurons is mediated by cochlear inner hair cells. The Journal of Physiology.
- A critical period of prehearing spontaneous Ca
2+
spiking is required for hair‐bundle maintenance in inner hair cells. The EMBO Journal.
- The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing. eLife, 4.
- A Lack of Immune System Genes Causes Loss in High Frequency Hearing but Does Not Disrupt Cochlear Synapse Maturation in Mice. PLoS ONE, 9(5), e94549-e94549.
- Exclusion of chromosome 15q21.1 in autosomal-recessive Weill-Marchesani syndrome in an inbred Lebanese family. Clinical Genetics, 58(6), 473-478.
Conference proceedings papers
- Complexity and integration in the control of inner-ear development. Genome Biology, Vol. 8(9) (pp 315-315)
- Single-cell RNA analysis of type I spiral ganglion neurons reveals a Lmx1a population in the cochlea. Frontiers in Molecular Neuroscience, 13. View this article in WRRO