Unresolved questions regarding human hereditary deafness.
Human hearing loss is a common neurosensory disorder about which many basic research and clinically relevant questions are unresolved. This review on hereditary deafness focuses on three examples considered at first glance to be uncomplicated, however, upon inspection, are enigmatic and ripe for future research efforts. The three examples of clinical and genetic complexities are drawn from studies of (i) Pendred syndrome/DFNB4 (PDS, OMIM 274600), (ii) Perrault syndrome (deafness and infertility) due to mutations of CLPP (PRTLS3, OMIM 614129), and (iii) the unexplained extensive clinical variability associated with TBC1D24 mutations. At present, it is unknown how different mutations of TBC1D24 cause non-syndromic deafness (DFNB86, OMIM 614617), epilepsy (OMIM 605021), epilepsy with deafness, or DOORS syndrome (OMIM 220500) that is characterized by deafness, onychodystrophy (alteration of toenail or fingernail morphology), osteodystrophy (defective development of bone), mental retardation, and seizures. A comprehensive understanding of the multifaceted roles of each gene associated with human deafness is expected to provide future opportunities for restoration as well as preservation of normal hearing.
Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.
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AU
Rehman
Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.
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TB
Friedman
Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.
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Griffith
D002352:Carrier Proteins / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D049071:Endopeptidase Clp / Q000235:genetics; D020690:GTPase-Activating Proteins; D006044:Goiter, Nodular / Q000235:genetics*; D023961:Gonadal Dysgenesis, 46,XX / Q000235:genetics*; D006228:Hand Deformities, Congenital / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008565:Membrane Proteins; D026901:Membrane Transport Proteins / Q000235:genetics; D009264:Nails, Malformed / Q000235:genetics; D009419:Nerve Tissue Proteins; D000076988:Sulfate Transporters
D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; C552551:TBC1D24 protein, human; C568646:ClpP protein, human; D049071:Endopeptidase Clp


CLPP

; 
SLC26A4
; 
TBC1D24
; Pendred syndrome; Perrault syndrome; enlarged vestibular aqueduct; hereditary deafness