KCNQ1 gene
The KCNQ1 gene encodes a protein that is a member of the KQT subfamily of potassium voltage-gated channel proteins and is located in the parietal membrane of the vascular striated limbic cells of the inner ear. This gene is located on chromosome 21q22.1-22.2 11p11.5. KCNQ1 is an important channel involved in the maintenance of cochlear potassium metabolism and cochlear potential, and mutations in this gene cause a decrease and loss of endolymphatic potential, resulting in impaired depolarization of hair cells;
This leads to type I Jervell and Lange-Nielsen syndrome, also known as congenital deafness and functional heart disease, which manifests as congenital deafness and long QT syndrome. Cochlear implantation has been shown to be effective.
TMC1 gene
The TMC1 (transmembrane channel-like 1) gene is located at 9q21.12 and has a genome consisting of 314,551 base pairs and 24 exons. Mutations in this gene are associated with DFNA36, DFNB7 and DFNB11. The function of the protein encoded by this gene is unknown, and in mice mutations in this gene can lead to degenerative changes in hair cells and are therefore thought to play a role in the development or maintenance of hair cells after birth.
Mutations in the TMC1 gene can cause both autosomal recessive deafness (DFNB7 and DFNB11) and autosomal dominant deafness (DFNA36), which manifests as progressive hearing loss. Cochlear implantation has been shown to be effective.
COCH gene
The COCH gene is a coagulation factor C homolog and is the only autosomal dominant non-syndromic deafness gene with vestibular symptoms. This gene encodes the Cochlin protein. The exact function of this protein is unknown, but immunohistochemical studies reveal that it is only expressed in tissues of mesodermal origin, such as the spiral ligament, spiral rim, and bone spiral plate channels in the cochlear canal, while tissues derived from neuroectodermal tissue lack Cochlin protein expression.
In addition, the sensory epithelium in the vestibular labyrinth and the fibroblasts and interstitium under the jugular crest are also highly expressed. Mutations in this gene can lead to non-syndromic deafness DFNA9, with a predominantly high-frequency, progressive hearing loss with abnormal vestibular function. Patients with this type of genetic deafness have mucopolysaccharide deposits in the cochlear canal and vestibular nerve, leading to degeneration of the dendritic fibers. Cochlear implantation has been shown to be effective.
LOXHD1 gene
The LOXHD1 gene encodes the protein “lipoxygenase homologous domain containing protein 1”, which plays a role in physiological processes such as calcium transport across the membrane, perception of mechanical stimuli and acoustoelectric conversion. Such a mutation can lead to deafness, which is characterized by mild to moderate moderate-to-high frequency hearing loss in childhood and adolescence, and later development of severe/very severe deafness. Cochlear implantation has been shown to be effective.
MYO15A gene
The MYO15A gene encodes myosin 15A, a protein that plays a crucial role mainly in hair cell actin organization; the protein interacts with whirlin and moves the latter to the apical attachment of the static cilia. Mutations in this gene cause autosomal recessive non-syndromic deafness. Cochlear implantation has been shown to be effective.
TECTA gene
The TECTA gene encodes the protein tectorin, which is one of the extracellular proteins of the lid membrane and is expressed in the otolithic membrane of the cochlea and vestibular system. Mutations in its gene can lead to autosomal dominant non-syndromic deafness or autosomal recessive non-syndromic deafness. Purely heterozygous mutations can lead to prespeech deafness with severe or profound deafness, and heterozygous mutations can lead to stable or progressive hearing loss. Cochlear implantation has good results.
ACTG1 gene
The ACTG1 gene encodes the ACTG1 protein, which belongs to the actin family, a family of highly conserved cellular scaffolding proteins that play an important role in almost all biological activities of eukaryotic cells. Cell differentiation, motility, cytosolic drinking, production of contractile force, and maintenance of cell morphology are dependent on the myosin Actin.
Based on the expression pattern, myosins are divided into several isoforms, such as muscle actin ACTA1 and ACTA2, which are expressed in transverse and smooth muscle, while non-muscle actin ACTG1 and ACTB are expressed in all cells in the cytoplasm. The gene is localized to 17q25.3, and mutations lead to Baraitser-Winter syndrome (a group of syndromes characterized by specific craniofacial structures, ocular defects and defects in neuronal migration) and DFNA20/26. Cochlear implantation is associated with good outcomes.
TMPRSS3 gene
The transmembrane protease serine 3 (TMPRSS3) is the first deafness-causing protease identified to date and is located on chromosome 21q22.3, spanning approximately 24 kb. It consists of 13 exons ranging in size from 44 bp (exon 7) to 889 bp (exon 13). The gene encodes the protein transmembrane serine protease 3. This protein belongs to the type II transmembrane serine protease family and is frequently expressed in the spiral ganglion, vascular striatum and Corti apparatus, but its function is not yet known.
Defects in the TMPRSS3 gene are the genetic basis of hereditary deafness DFNB8/10. Mutations in this gene cause severe/very severe deafness in patients, but the age of onset, severity and rate of progression vary. The results after cochlear implantation are good.
MYH9 gene
The MYH9 gene encodes the protein MYH9, a component of the myosin complex, which is important for maintaining T-cell morphology independent of synaptic structure. The phosphorylation of the multimerization domain of MYH9 gene suggests that actin plays a key role in the “termination” response of T-cell recognition of antigen.
MYH9 mutations are associated with a variety of disorders and can cause, in addition to DFNA17, Epstein syndrome, Fichtner syndrome (familial thrombocytopenia), macrothrombocytopenia combined with progressive sensorineural deafness, May-Heinrich anomaly, and Sebastan syndrome (abnormal thrombocytopenia), which are a rare group of autosomal dominant disorders. They are characterized by thrombocytopenia, increased platelet size, neutrophil inclusion bodies, hearing loss, cataracts, and renal impairment. The outcome after cochlear implantation is uncertain.
POU3F4 gene
The POU3F4 gene is the only gene related to non-syndromic deafness that has been cloned from the X chromosome, and it encodes a protein called “POU structural domain class 3 transcription factor 4”, which plays an important role in cochlear morphogenesis. ～The POU3F4 transcription factor is composed of 361 amino acids, of which amino acids 194 to 260 constitute the specific structural domain, while amino acids 276 to 335 constitute the homologous structural domain.
This gene mutation can lead to X-linked hereditary deafness, which manifests as progressive sensorineural deafness, and can also lead to conductive deafness if accompanied by stapes fixation. The outcome after cochlear implantation is uncertain.
PCDH15 gene
The PCDH15 gene encodes a protein called pro-calmodulin 15, which is located at 10q21.1. It is a member of the calmodulin family and encodes a class of membrane binding proteins that regulate intercellular adhesion. Two calmodulin proteins, CDH23 and PCDH15, are associated with a genetic pattern of deafness, interacting to form apical links and extracellular filaments that connect the static cilia and affect the machine-to-electrical transduction channel.
Mutations in this gene can lead to DFNB23, USH1F and Usher syndrome 1D/F, manifesting as congenital very severe sensorineural deafness, which can be associated with vestibular loss and progressive retinitis pigmentosa. The outcome after cochlear implantation is uncertain.
CHD7 gene
The CHD7 gene encodes a protein called “chromatin domain decapping enzyme DNA-binding protein 7”, which is located at 8q12.2 and is a transcriptional regulator that plays an important role in inner ear development and is associated with Charge syndrome and hypogonadotropic hypogonadism with or without anosmia syndrome. Mutations in this gene can lead to inner ear malformations, posterior nostril atresia, congenital heart disease, genitourinary abnormalities, retinal malformations, and developmental delays. Poor outcome after cochlear implantation.
IMM8A gene
The IMM8A gene encodes the protein “Tim8A, a subunit of mitochondrial endosomal input translocase”. Mutations in this gene can lead to Mohr-Tranebjaerg syndrome, which is a recessive neurodegenerative syndrome with progressive post-speech sensorineural deafness in childhood as the first symptom, followed by a series of multiple neurological pathologies. The outcome after cochlear implantation is poor.
PLVK gene
The PLVK gene encodes the protein Pejvakin, which is expressed in spiral ganglion neurons and may be involved in action potential conduction or intracellular transport. Mutations in this gene can lead to auditory neuropathy. Because the lesion is often not located in the inner hair cells or synapses, cochlear implantation has poor outcomes.
Genes associated with Waardenburg syndrome
Waardenburg syndrome (WS) is a new syndrome first described in the literature in 1951 by Waardenburg, a Dutch ophthalmologist and geneticist, as an aberration of chromosome 2. There are six genes associated with WS: PAX3, MITF, SNAI2, EDNRB, END3 and SOX10, of which PAX3, MITF, SNAI2 and SOX10 are transcription factors and EDNRB and END3 are signaling molecules.
WS, also known as medial canthal deafness syndrome or deaf white hair ophthalmopathy syndrome, is usually characterized by sensorineural deafness and abnormal pigment distribution in the iris, hair and skin, also known as hearing-pigmentation syndrome, but has no effect on vision. Cochlear implantation has good results.