17 results about "Hereditary deafness" patented technology

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 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.

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.

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.