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Nonsyndromic Hearing Loss And Deafness
Nonsyndromic deafness is hearing loss that is not associated with other signs and symptoms. In contrast, syndromic deafness involves hearing loss that occurs with abnormalities in other parts of the body. Genetic changes are related to the following types of nonsyndromic deafness. * DFNA: nonsyndromic deafness, autosomal dominant * DFNB: nonsyndromic deafness, autosomal recessive * DFNX: nonsyndromic deafness, X-linked * nonsyndromic deafness, mitochondrial Each type is numbered in the order in which it was described. For example, DFNA1 was the first described autosomal dominant type of nonsyndromic deafness. Mitochondrial nonsyndromic deafness involves changes to the small amount of DNA found in mitochondria, the energy-producing centers within cells. Most forms of nonsyndromic deafness are associated with permanent hearing loss caused by damage to structures in the inner ear. The inner ear consists of three parts: a snail-shaped structure called the cochlea that helps process ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hearing Impairment
Hearing loss is a partial or total inability to hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to acquire spoken language, and in adults it can create difficulties with social interaction and at work. Hearing loss can be temporary or permanent. Hearing loss related to age usually affects both ears and is due to cochlear hair cell loss. In some people, particularly older people, hearing loss can result in loneliness. Deaf people usually have little to no hearing. Hearing loss may be caused by a number of factors, including: genetics, ageing, exposure to noise, some infections, birth complications, trauma to the ear, and certain medications or toxins. A common condition that results in hearing loss is chronic ear infections. Certain infections during pregnancy, such as cytomegalovirus, syphilis and rubella, may also cause hearing loss in the child ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
COCH Protein
Cochlin is a protein that in humans is encoded by the ''COCH'' gene. It is an extracellular matrix (ECM) protein highly abundant in the cochlea and vestibule of the inner ear, constituting the major non-collagen component of the ECM of the inner ear. The protein is highly conserved in human, mouse, and chicken, showing 94% and 79% amino acid identity of human to mouse and chicken sequences, respectively. Structure Cochlin contains three protein domains: an N-terminal LCCL domain, and two copies of Von Willebrand factor type A domains. Function The gene is expressed in spindle-shaped cells located along nerve fibers between the auditory ganglion and sensory epithelium. These cells accompany neurites at the habenula perforata, the opening through which neurites extend to innervate hair cells. This and the pattern of expression of this gene in chicken inner ear paralleled the histologic findings of acidophilic deposits, consistent with mucopolysaccharide ground substance, in t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
POU3F4
POU domain, class 3, transcription factor 4 is a protein that in humans is encoded by the ''POU3F4'' gene found on the X chromosome. POU3F4 is involved in the patterning of the neural tube and both the paraventricular and supraoptic nuclei of the hypothalamus in the developing embryo. During development, POU3F4 is also expressed in the mesenchyme of the periotic bone surrounding the inner ear. A “knockout” mice model displayed that alteration to the POU3F4 gene interrupted this mesenchymal cell differentiation in the superior semicircular canal. The deformities observed in mice were similar to those in humans with X-linked non-syndromic deafness (DFN-3). Clinical significance Genetic testing on various persons has confirmed that mutations of the POU3F4 gene cause X-linked non-syndromic deafness (DFN-3). These known mutations include: * Missense mutation causing the substitution of amino acid glycine for glutamic acid at position 216 * A deletion of the POU3F4 gene and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PCDH15
Protocadherin-15 is a protein that in humans is encoded by the ''PCDH15'' gene. Function This gene is a member of the cadherin superfamily. Family members encode integral membrane proteins that mediate calcium-dependent cell-cell adhesion. The protein product of this gene consists of a signal peptide, 11 extracellular calcium-binding domains, a transmembrane domain and a unique cytoplasmic domain. It plays an essential role in maintenance of normal retinal and cochlear function. It is thought to interact with CDH23 to form tip-link filaments. Clinical significance Mutations in this gene have been associated with hearing loss, which is consistent with its location at the Usher syndrome Usher syndrome, also known as Hallgren syndrome, Usher–Hallgren syndrome, retinitis pigmentosa–dysacusis syndrome or dystrophia retinae dysacusis syndrome, is a rare genetic disorder caused by a mutation in any one of at least 11 genes result ... type 1F (USH1F) critical region on chr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
OTOF
Otoferlin is a protein that in humans is encoded by the ''OTOF'' gene. Function Mutations in this gene are a cause of neurosensory nonsyndromic recessive deafness, DFNB9. The short form of the encoded protein has three C2 domains, a single carboxy-terminal transmembrane domain found also in the C. elegans spermatogenesis factor FER-1 and human dysferlin, while the long form has six C2 domains. Otoferlin homologous proteins in humans that have been shown to be associated with human diseases are dysferlin and myoferlin. Both dysferlin and myoferlin have seven C2 domains. C2A in otoferlin's longer form with six C2 domains is structurally similar to dysferlin C2A. However, the loop 1 in calcium binding site of otoferlin C2A is significantly shorter than the homologous loop in dysferlin and myoferlin C2A domains. Therefore, it is unable to bind to calcium. Otoferlin C2A is also unable to bind to phospholipids and hence it is structurally and functionally different from other C2 doma ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MYO7A
Myosin VIIA is protein that in humans is encoded by the ''MYO7A'' gene. Myosin VIIA is a member of the unconventional myosin superfamily of proteins. Myosins are actin binding molecular motors that use the enzymatic conversion of ATP - ADP + inorganic phosphate (Pi) to provide the energy for movement. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. Myosin VIIA is an unconventional myosin with the longest tail (1360 aa). The tail is expected to dimerize, resulting in a two-headed molecule. Unconventional myosins have diverse functions in eukaryotic cells and are primarily thought to be involved in the movement or linkage of intra-cellular membranes and organelles to the actin cytoskeleton via interactions mediated by their highly divergent tail domains. MYO7A is expressed in a number of mammalian tissues, including testis, ki ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MYO6
Unconventional myosin-VI, is a protein that in humans is coded for by ''MYO6''. Unconventional myosin-VI is a myosin molecular motor involved in intracellular vesicle and organelle transport. Structure Human myosin-VI contains a N-terminal myosin head domain (residues 59–759), two coiled coil motifs (residues 902–984 and 986–1009 respectively), and a C-terminal myosin VI cargo binding domain (residues 1177–1267). Function Unconventional myosin-VI is unique because it travels in the opposite direction of other myosins, towards the negative end of actin filaments. Myosin-VI follows the same structure as other myosin but with two unique "inserts" allowing for its diversified properties. One insert is called the "reverse gear" and is responsible for its movement towards the negative end of actin filaments. The reverse gear is located on the neck region of the myosin and acts as a reorienting device for the lever arm to move backwards after myosin movement. The second inse ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MYO15A
Myosin-XV is a protein that in humans is encoded by the ''MYO15A'' gene. Gene Read-through transcript containing an upstream gene and this gene have been identified, but they are not thought to encode a fusion protein. Several alternatively spliced transcript variants have been described, but their full length sequences have not been determined. Function This gene encodes an unconventional myosin. This protein differs from other myosins in that it has a long N-terminal extension preceding the conserved motor domain. Studies in mice suggest that this protein is necessary for actin organization in the hair cells of the cochlea. Clinical significance Mutations in this gene have been associated with profound, congenital, neurosensory, nonsyndromic deafness. This gene is located within the Smith–Magenis syndrome Smith–Magenis Syndrome (SMS), also known as 17p- syndrome, is a microdeletion syndrome characterized by an abnormality in the short (p) arm of chromosome ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
KCNQ4
Potassium voltage-gated channel subfamily KQT member 4, also known as voltage-gated potassium channel subunit Kv7.4, is a protein that in humans is encoded by the ''KCNQ4'' gene. Function The protein encoded by this gene forms a potassium channel that is thought to play a critical role in the regulation of neuronal excitability, particularly in sensory cells of the cochlea. The encoded protein can form a homomultimeric potassium channel or possibly a heteromultimeric channel in association with the protein encoded by the KCNQ3 gene. Clinical significance The current generated by this channel is inhibited by muscarinic acetylcholine receptor M1 and activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of nonsyndromic sensorineural deafness type 2 (DFNA2), an autosomal dominant form of progressive hearing loss. Two transcript variants encoding different isoforms have been found for this gene. Ligands * ML213: KCNQ2/Q4 channel opener. See ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GJB6
Gap junction beta-6 protein (GJB6), also known as connexin 30 (Cx30) — is a protein that in humans is encoded by the ''GJB6'' gene. Connexin 30 (Cx30) is one of several gap junction proteins expressed in the inner ear. Mutations in gap junction genes have been found to lead to both syndromic and nonsyndromic deafness. Mutations in this gene are associated with Clouston syndrome (i.e., hydrotic ectodermal dysplasia). Function The connexin gene family codes for the protein subunits of gap junction channels that mediate direct diffusion of ions and metabolites between the cytoplasm of adjacent cells. Connexins span the plasma membrane 4 times, with amino- and carboxy-terminal regions facing the cytoplasm. Connexin genes are expressed in a cell type-specific manner with overlapping specificity. The gap junction channels have unique properties depending on the type of connexins constituting the channel. upplied by OMIMref name="entrez"/> Connexin 30 is prevalent in the two distin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GJB2
Gap junction beta-2 protein (GJB2), also known as connexin 26 (Cx26) — is a protein that in humans is encoded by the ''GJB2'' gene. Clinical significance Defects in this gene lead to the most common form of congenital deafness in developed countries, called DFNB1 (also known as connexin 26 deafness or ''GJB2''-related deafness). One fairly common mutation is the deletion of one guanine from a string of six, resulting in a frameshift and termination of the protein at amino acid number 13. Having two copies of this mutation results in deafness. Connexin 26 also plays a role in tumor suppression through mediation of the cell cycle. The abnormal expression of Cx26, correlated with several types of human cancers, may serve as a prognostic factor for cancers such as colorectal cancer, breast cancer, and bladder cancer. Furthermore, Cx26 over-expression is suggested to promote cancer development by facilitating cell migration and invasion and by stimulating the self-perpetuation ab ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
EYA4
Eyes absent homolog 4 is a protein that in humans is encoded by the ''EYA4'' gene. This gene encodes a member of the eyes absent (EYA) subfamily of proteins. The encoded protein may act as a transcriptional activator and be important for continued function of the mature organ of Corti The organ of Corti, or spiral organ, is the receptor organ for hearing and is located in the mammalian cochlea. This highly varied strip of epithelial cells allows for transduction of auditory signals into nerve impulses' action potential. Transd .... Mutations in this gene are associated with postlingual, progressive, autosomal dominant hearing loss at the deafness, autosomal dominant nonsyndromic sensorineural 10 locus. Three transcript variants encoding distinct isoforms have been identified for this gene. References Further reading * * * * * * * * * * * {{gene-6-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
