22 results about "Hereditary deafness" patented technology

The invention belongs to the technical field of establishment of CNVs pathogenic mechanism models, and discloses a molecular mechanism of CNVs mutation and an establishment method of a CNVs pathogenic mechanism model.Deafness predeaf people CNVs are taken as an entry point, common CNVs in Chinese people with normal hearing are combined, and through establishment of researched deafness gene CNVs characteristics, mutation mechanism and pathogenic mechanism models, the molecular mechanism of CNVs mutation and the establishment method of the CNVs pathogenic mechanism model are established. The important function and significance of the copy number variation in hereditary hearing loss are explored, and meanwhile molecular diagnosis and prevention and treatment of the copy number variation in hereditary hearing loss are guided. Summarizing hot spot positions, sequences and structural characteristics of the deafness gene CNVs; the distribution and characteristic difference between pathogenic CNVs and common CNVs polymorphisms is summarized, and molecular diagnosis of CNVs related diseases is guided; and a molecular mechanism of deafness gene CNVs mutation and a deafness gene CNVs pathogenic mechanism model are explored.

The invention relates to the technical field of biology, in particular to a construction method of an Elmod3 gene mutation mouse model. Based on clinical data of hereditary deafness family patients, ELMOD3c.512Agt is found; g abnormal mutation can cause delayed progressive sensorineural deafness of a patient. According to the invention, a molecular marker with Elmod3c.512Agt is constructed; the G point mutation mouse model is consistent with the mutation site of a patient, and after the mouse is born, the disease progresses under the normal feeding environment and the natural growth rule, so that the experiment conditions of the disease research of the model mouse are closer to the real disease development of family patients, and a researcher can deeply research how the ELMOD3 gene mutation causes deafness. And a foundation is laid for functional research and subsequent gene therapy research of the ELMOD3 in an inner ear auditory system.

The invention relates to the field of molecular biology and medical genetics, and particularly discloses a method for regulating and controlling transport of a TMC1 plasma membrane through TRAPPC3 and application of the method in an auditory function. The TMC1 is a core protein of a hair cell mechanical electrotransduction (MET) channel, and abnormal positioning of the TMC1 is closely related to hereditary hearing loss. The research finds that the transport protein particle compound component TRAPPC3 can specifically interact with the TMC1 protein to promote the TMC1 to be correctly positioned to a cell membrane from cytoplasm, so that the auditory function of hair cells is maintained. According to the method for regulating and controlling the positioning of the TMC1 from the cytoplasm to the cell membrane through co-expression of the TRAPPC3, a functional TMC1 channel can be reconstructed in a heterologous system, and the method is suitable for deafness molecular mechanism research, drug screening and gene therapy strategy development. According to the invention, the TRAPPC3-TMC1 interaction mechanism is provided for the first time, and a new intervention target is provided for hereditary hearing loss treatment.

The invention particularly relates to a primer probe and a kit for detecting the copy number of a GJB2 gene of a non-syndromic deafness patient by using microdroplet digital PCR (Polymerase Chain Reaction), and application of the primer probe and the kit. The primer probe combination provided by the invention comprises a target gene detection primer pair, a target gene detection probe, an upstream primer of a reference gene, a downstream primer of the reference gene and a probe of the reference gene, and the sequence information of the primer probe combination is shown as SEQ ID NO.6-11; the invention also provides a kit for detecting the copy number of the GJB2 gene of a non-syndromic deafness patient. When the primer probe combination and the kit provided by the invention are applied to detection of copy number variation of the GJB2 gene of a patient with non-syndromic deafness, the accuracy of hereditary deafness detection is remarkably improved; whether GJB2 gene expression is abnormal or not is judged in an auxiliary mode according to the judgment result, disease prognosis is evaluated, potential treatment drugs are screened, genetic counseling services are provided or personalized medical schemes are formulated, and the method has wide application prospects.

The present invention relates to a polypeptide which is a temperature-modulated ion channel, wherein said ion channel is a channel comprising four subunits which associate to form a homo- or hetero-tetramer, preferably is a potassium channel, wherein said polypeptide comprises at least one peptide comprising at least one portion of one of said subunits and a portion of the cytoplasmic C-terminal domain of the bacterial voltage-gated sodium channel BacNav, wherein said portion comprises at least one mutation in one of the amino acids in position 267, 271 or 274, wherein said numbering is read with reference to the voltage-gated sodium channel BacNav, SEQ ID NO: 5. The present invention further relates to the use of said polypeptide in the treatment of a condition modulated by potassium channel activity, selected from the group comprising: neuromyotonia, episodic ataxia type 1, hereditary deafness syndromes, benign familial neonatal seizures and periodic hypokalemic paralysis, neuropathic pain, diabetic neuropathic pain, trauma (thoracic surgery), glioblastoma, skin diseases, in particular originating from keratinocyte dysfunctions.

The invention discloses a primer group for detecting hereditary hearing loss gene locus polymorphism, a kit and a detection method thereof. The primer group comprises a multiple PCR amplification primer and a UEP primer used for a single base extension reaction, multiple PCR amplification is firstly carried out, SAP purification is then carried out, the extension reaction is then carried out, nucleic acid mass spectrometry detection is carried out on an extension product, and related genotype information is obtained. The method has the advantages of high accuracy, high flux, low cost and short period, 96 samples or 384 samples can be detected in one batch, only 8-10 hours are needed, the time is short, and the price is low. 27 hereditary deafness gene variation sites can be detected, 9 genes are involved, the coverage range is wider, and the misdiagnosis risk caused by incomplete detection sites is reduced. The method has high accuracy, sensitivity and repeatability, and the detection result has important guidance and research value for auxiliary diagnosis and treatment of hereditary hearing loss.

The invention relates to the field of quality testing, and discloses a reagent detection method for a hereditary hearing loss high-frequency mutation site, which is used for providing a reliable measurement technical means for quality detection of a hereditary hearing loss high-frequency mutation site detection reagent. Comprising the following steps: acquiring original fluorescence physical signals of a reagent solution under a plurality of optical detection channels by using an optical detection instrument; performing photoelectric conversion and standardization on the repeated physical detection signals, and generating a weighted synthesis signal in combination with an expected response weight so as to evaluate the overall optical luminescence physical stability of the reagent solution; a correlation network between physical response signals of different detection channels is constructed, the luminescence dynamics consistency in a reagent solution system is quantified by calculating the global efficiency of the correlation network, and the fluctuation amplitude of the physical luminescence state of the reagent solution is accurately measured. According to the invention, comprehensive, sensitive and anti-interference closed-loop testing of real physical properties of the reagent materials can be realized.

The present disclosure belongs to the field of hearing impairment, and particularly relates to a genetic deafness detection system, a marker or a probe, a drug and applications. It is disclosed that Taperin forms a ring structure at the tapered region of the hair cell stereocilia root; it is determined that Taperin-Clic5-Ptprq forms a ring complex structure at the stereocilia root; the Taperin-Clic5-Ptprq ring complex structure is crucial for maintaining hearing, and its destruction will cause severe hearing loss; the expression amount of Taperin is crucial for maintaining and stabilizing the ring structure; the hearing loss caused by the destruction of the ring structure can be treated by gene delivery.

The application discloses a TECTA gene mutant and application thereof, and relates to the technical field of molecular biology. The nucleotide of the TECTA gene mutant has a c.235G>C mutation relative to the nucleotide of a wild type TECTA gene, and the encoded protein has a p.Val79Leu mutation relative to the protein expressed by the wild type TECTA gene. The application also provides application of a primer pair for detecting the TECTA gene mutant in preparation of a DFNA8 / 12 pathogenic gene diagnostic reagent or a DFNA8 / 12 pathogenic gene diagnostic kit. The TECTA mutant gene provided by the application is a pathogenic variation of autosomal dominant deafness 8 / 12, and the diagnostic reagent or the kit can be used for genetic deafness screening, has important clinical application value for filling the blank of the prior art and promoting precise diagnosis and treatment of TECTA related genetic deafness.

The invention belongs to the technical field of molecular biology, and particularly relates to a POU3F4 gene mutant and application thereof. The nucleotide of the POU3F4 gene mutant has c.703Tgt relative to the nucleotide of a wild type POU3F4 gene; a mutation. The POU3F4 mutant gene provided by the invention is a novel pathogenic variation of type 2 X-linked hereditary hearing loss, and the pathogenic variation can be used for screening DFNX2 female carriers which are asymptomatic or slight in phenotype but difficult to find in daily life; and gene diagnosis is carried out on male patients, so that a scientific operation scheme is provided for hearing intervention.

The invention belongs to the technical field of hereditary deafness molecular diagnosis, and particularly relates to a deafness gene therapy related gene capture probe set, a detection method and application, the capture probe set comprises any one nucleotide sequence in SEQ ID NO.1-SEQ ID NO.404; the detection method comprises the following steps: carrying out hybrid capture on a nucleic acid sample to be detected by using the capture probe group; constructing a library for the captured target sequence, and performing high-throughput double-end sequencing; comparing the sequencing result with a reference genome, and identifying mutation of genes related to deafness gene therapy; the invention also discloses application of the capture probe group for the deafness gene therapy related genes in preparation of detection products for deafness genetic screening, deafness cause diagnosis, deafness genetic typing or gene therapy decision. Compared with the prior art, the gene capture probe set for deafness related to gene therapy is designed, the problem of non-uniform coverage of conventional sequencing in such areas is solved, and the whole genome capture uniformity and efficiency are improved.

The invention discloses a deafness gene detection kit based on a molecular beacon and a medium probe and application, and relates to the technical field of molecular biology. The kit is used for single-tube detection of 15 mutation sites on four hereditary deafness genes, the detection kit comprises freeze-dried microspheres serving as standardized solid-state reagent units, the freeze-dried microspheres comprise specific primers, specific molecular beacons and specific medium probes, nucleotide sequences of the specific primers are shown as SEQ ID NO.35-SEQ ID NO.50, and nucleotide sequences of the specific molecular beacons and the specific medium probes are shown as SEQ ID NO.35-SEQ ID NO.50. The nucleotide sequences of the specific molecular beacons are as shown in SEQ ID NO.1 to SEQ ID NO.4, and the nucleotide sequences of the specific medium probes are as shown in SEQ ID NO.5 to SEQ ID NO.34. Compared with a traditional PCR technology, a chip technology and the like, the detection method provided by the invention can realize single-tube detection of different deafness genes, is simpler to operate, short in detection period and low in cost, and remarkably improves the detection sensitivity and accuracy.

According to the kit for detecting the hereditary hearing loss related genes based on the hybridization capture method, the hybridization capture method and the application, the kit comprises a probe pool of capture probes, and the capture probes are used for hybridizing and capturing the hereditary hearing loss related genes. The kit disclosed by the invention has the beneficial effects that when the kit is used for constructing a DNA library, the initial quantity of a template can be as low as 10ng, and enzyme digestion breaking, terminal filling and A tail adding are completed in one system, so that the consumed time is short, and the efficiency is high; secondly, the number of index pairs of the kit is up to 384, and 384 libraries can be constructed at the same time and can be used for sequencing on a machine together; in addition, according to a rapid hybridization system of the kit, the shortest hybridization time can reach 15 min, and the efficiency of common overnight hybridization can be achieved. The size of the finally obtained library fragment is about 300-500bp, and the library fragment can be compatible with various sequencing platforms of illumina for sequencing.

The present invention belongs to the field of gene therapy within the medical field, and specifically involves the use of overexpression of normal genes to restore hearing in patients with hereditary deafness caused by gene mutation or deletion. The present invention provides a dual-vector system for expressing the OTOF protein, comprising two nucleotide sequences: a first nucleotide sequence comprising two ITR sequences and a gene expression cassette inserted between the ITR sequences; and a second nucleotide sequence comprising two ITR sequences and a gene expression cassette inserted between the ITR sequences. The gene expression cassette of the first nucleotide sequence comprises a promoter, an OTOF N-terminal coding sequence, an intein N-terminal coding sequence, and polyA; and the gene expression cassette of the second nucleotide sequence comprises a promoter, an intein C-terminal coding sequence, an OTOF C-terminal coding sequence, and polyA. Also provided is an adeno-associated virus packaged by the aforementioned vector. The vector and virus can be used in the field of large-gene dual-vector delivery for gene therapy for deafness to restore hearing in both ears through unilateral administration.

The application particularly relates to a primer probe, a kit and application for detecting the GJB2 gene copy number of a non-syndromic hearing loss patient by using microdroplet digital PCR. The primer probe combination provided by the application comprises a target gene detection primer pair, a target gene detection probe, an upstream primer of a reference gene, a downstream primer of the reference gene and a reference gene probe, and the sequence information is shown as SEQ ID NO. 6-11; and the application further provides a kit for detecting the GJB2 gene copy number of a non-syndromic hearing loss patient. The primer probe combination and the kit provided by the application are applied to the detection of the GJB2 gene copy number variation of a non-syndromic hearing loss patient, and the accuracy of the detection of genetic hearing loss is significantly improved; according to the determination result, it is determined whether the GJB2 gene expression is abnormal or not, the disease prognosis is evaluated, potential therapeutic drugs are screened, genetic counseling services are provided or individualized medical schemes are formulated, and the application has a wide application prospect.

A disclosed blending device based on hereditary hearing loss gene detection comprises a box body, a rotating disc and a conversion assembly, the conversion assembly comprises a moving groove formed in the box body, a sliding column coaxially connected with the bottom end of the rotating disc is slidably clamped in the moving groove, a guide groove is formed in the bottom end of the sliding column, and a suspension is arranged at the top end of the inner wall of the box body; a first bevel gear is rotationally clamped at the bottom end of the suspension, a motor is arranged on the inner bottom wall of the box body, the output shaft end of the motor is coaxially connected with a second bevel gear through a coupler, the first bevel gear is meshed with the second bevel gear, the top end of the first bevel gear is coaxially connected with a guide plate, the guide plate is clamped in the guide groove, and a controller arranged on the suspension can drive the sliding column to move. The conversion assembly arranged in the device can be used in cooperation with the rotating disc, so that the device can achieve vortex oscillation and centrifugal oscillation at the same time, and when the oscillation mode needs to be adjusted, the controller drives the sliding column to move in the moving groove, and the position relation between the sliding shaft and the axis of the first bevel gear is changed.

The invention discloses application of a substance for detecting an OPA1 mutation site in preparation of a product for diagnosing syndrome-type hereditary hearing loss. The OPA1 mutation site is any one of the following nucleotides shown as the 1333rd site, the 1555th site, the 2635th site and the 2639th site of the OPA1 gene. According to the invention, three OPA1 gene pathogenic mutation sites related to syndrome-type hereditary hearing loss are found for the first time, and whether a to-be-detected person suffers from syndrome-type hereditary hearing loss or not can be effectively judged and an individual susceptible to syndrome-type hereditary hearing loss can be screened by detecting whether the three mutation sites in the to-be-detected person are mutated or not; meanwhile, an OPA1 gene mutant can be constructed on the basis of the three mutation sites so as to be used for screening drugs for treating syndrome-type hereditary hearing loss. Genetic basis is provided for developing molecular diagnosis of hereditary hearing loss, and a new detection site is provided for diagnosis or treatment of the hereditary hearing loss.

The invention discloses a primer group, a kit and a method for detecting STRC gene variation and application. The primer group comprises one or more of primer groups 1-8. Targeted enrichment based on the primer group is combined with three-generation sequencing, so that single nucleotide variation, insertion / deletion, exon copy number variation and structural variation caused by non-allelic homologous recombination of the STRC gene can be comprehensively and accurately detected, the cis-trans relationship between the variations can be defined, and an efficient tool is provided for diagnosis of hereditary hearing loss.

The present invention relates to a dual-vector system for expressing MYO7A protein, comprising a first nucleic acid vector and a second nucleic acid vector wherein the first nucleic acid vector comprises a first nucleotide sequence; the second nucleic acid vector comprises a second nucleotide sequence; the first nucleotide sequence comprises an expression cassette inserted between two first ITR sequences; the second nucleotide sequence comprises an expression cassette inserted between two second ITR sequences; the expression cassette of the first nucleotide sequence comprises a promoter, an N-terminal coding sequence of MYO7A, an N-terminal coding sequence of intein and polyA; the expression cassette of the second nucleotide sequence comprises a promoter, a C-terminal coding sequence of intein, a C-terminal coding sequence of MYO7A and polyA. The invention also relates to a packaging carrier system of the adeno-associated virus, a packaging method of the adeno-associated virus and the adeno-associated virus obtained by the method. The dual vector system or adeno-associated virus for expressing the MYO7A protein of the invention can be used for gene therapy, especially for the treatment of hearing loss, such as for the treatment of USH1B associated with MYO7A mutation, autosomal recessive hereditary deafness DFNB2, autosomal dominant hereditary deafness DFNA11.

The invention provides a spontaneous deafness disease rat model constructed based on a cytosine base editor. The rat model provided by the invention lays a foundation for screening a base editor human source treatment target spot for gene therapy of Gjb2V37X point mutation human hereditary deafness, delivery of AAV and other vectors to a human Gjb2 overexpression vector and a base editor, clinical drug screening and a pathogenic mechanism of point mutation deafness on a V37 site on a human Gjb2 gene.

The application relates to a primer group, a kit and a method for detecting a plurality of disease-related gene mutation types. The application can simultaneously detect genetic deafness, thalassemia and spinal muscular atrophy disease-related gene mutation types, only needs one tube, and can simultaneously detect clinically common known pathogenic SNPs, INDELs and copy number variations in one experiment, thereby significantly improving the detection efficiency of the three diseases and the standardization degree of clinical detection. The primer group comprises: 1) a primer for detecting genetic deafness gene mutation types, as shown in SEQ ID NO: 1-30; 2) a primer for detecting thalassemia gene mutation types, as shown in SEQ ID NO: 31-340; 3) a primer for detecting spinal muscular atrophy gene mutation types, as shown in SEQ ID NO: 341-350; and 4) a primer for detecting a beta-actin housekeeping gene, as shown in SEQ ID NO: 351-352.

The present invention relates to a dual-vector system for expressing an MYO7A protein. The dual-vector system comprises a first nucleic acid vector and a second nucleic acid vector, wherein the first nucleic acid vector comprises a first nucleotide sequence, and the second nucleic acid vector comprises a second nucleotide sequence. The first nucleotide sequence comprises an expression cassette inserted between two first ITR sequences, and the second nucleotide sequence comprises an expression cassette inserted between two second ITR sequences. The expression cassette of the first nucleotide sequence comprises a promoter, an N-terminal coding sequence of MYO7A, an N-terminal coding sequence of intein, and polyA; and the expression cassette of the second nucleotide sequence comprises a promoter, a C-terminal coding sequence of intein, a C-terminal coding sequence of MYO7A, and polyA. The present invention also relates to a packaging vector system of an adeno-associated virus, a method for packaging an adeno-associated virus, and an adeno-associated virus obtained thereby. The dual-vector system for expressing the MYO7A protein, or the adeno-associated virus can be used for gene therapy, especially for the treatment of hearing loss, such as for the treatment of MYO7A-mutation-related USH1B, autosomal recessive hereditary deafness DFNB2 and autosomal dominant hereditary deafness DFNA11.