CN-119351411-B - TBC1D24 gene mutant and application thereof

CN119351411BCN 119351411 BCN119351411 BCN 119351411BCN-119351411-B

Abstract

The invention relates to the technical field of gene diagnosis, and particularly discloses a TBC1D24 gene mutant and application thereof. Specifically disclosed is any TBC1D24 gene mutant, namely nucleic acid TBC1D24, which has c.677_680delCCCG mutation and c.8235C > T mutation compared with wild type TBC1D24 gene with the sequence of SEQ ID NO. 1, and polypeptide TBC1D24, which has p.A226Gfs 28 mutation and p.A244V mutation compared with protein encoded by wild type TBC1D24 gene with the sequence of SEQ ID NO. 2. Also discloses the application of the TBC1D24 gene mutant in screening the familial infant myoclonus epilepsy. The invention widens the pathogenic gene spectrum of familial infant myoclonus epilepsy, strengthens the knowledge of clinicians on the diseases, provides experience for screening and diagnosing the diseases clinically, is particularly convenient for screening before pregnancy, provides research direction and new theoretical basis for early diagnosis and effective treatment of the diseases, and also practically provides new molecular targets for developing and treating specific drugs for the diseases.

Inventors

SONG JINLIAN
Hao Guiliang
ZHAO LIN
YU MEIQIN
GUO MINGZHEN

Assignees

青岛市妇女儿童医院（青岛市妇幼保健院、青岛市残疾儿童医疗康复中心、青岛市新生儿疾病筛查中心）

Dates

Publication Date: 20260508
Application Date: 20240522

Claims (4)

A TBC1D24 gene mutant characterized in that the TBC1D24 gene mutant is a TBC1D24 composite mutant and has a composite heterozygous mutation of: A nucleic acid TBC1D24-1 having a fragment of interest therein and having a mutation of c.677-680 delCCCG as compared to the wild-type TBC1D24 gene having the sequence SEQ ID NO. 1, A nucleic acid TBC1D24-2 having a fragment of interest therein and having a c.731c > T mutation compared to the wild-type TBC1D24 gene having the sequence SEQ ID No. 1.
2. The application of the reagent for specifically detecting TBC1D24 gene mutant in claim 1 in preparing products for screening family infant myoclonus epilepsy is characterized in that, The product for screening the familial infant type myoclonus epilepsy is a product for screening the crowd suffering from familial infant type myoclonus epilepsy or a product for screening the carrier of the frequently-dyeing recessive genetic familial infant type myoclonus epilepsy diseased gene.
3. The use of the reagent for specifically detecting TBC1D24 gene mutant according to claim 2 for preparing a product for screening family infant myoclonus epilepsy, The reagent for specifically detecting the TBC1D24 gene mutant according to claim 1 is at least one of a probe and a primer specific to the TBC1D24 gene mutant.
4. The use of the reagent for specifically detecting TBC1D24 gene mutant according to claim 1 for preparing a product for screening family infant myoclonus epilepsy according to claim 3, The primer is at least a primer pair F-CATGACGTTTGGGGACCTGG and R-CCGGCGACCTACCTCTTCTG.

Description

TBC1D24 gene mutant and application thereof The application relates to a gene mutant and application thereof, in particular to a divisional application of Chinese application patent application with the application number of 202410635750.X and the application date of 2024, 5 and 22. Technical Field The invention relates to the technical field of gene diagnosis, in particular to a TBC1D24 gene mutant and application thereof. Background Familial infantile myoclonus epilepsy (OMIM: 605021), AR, diseases described by myoclonus epilepsy, familial infantile epilepsy, also known as familial infantile myoclonus epilepsy, familial infantile myoclonus epilepsy occurring in early infancy, manifested by myoclonus epilepsy, febrile convulsion, tonic-clonic seizures, good response to treatment with antiepileptic drugs, normal development of the intellectual and neurological systems, its clinical phenotypes: dysarthria, generalized tonic-clonic seizures, systemic myoclonus seizures, febrile convulsions, onset of infancy, differences in manifestations, focal seizures. An important gene associated with familial infantile myoclonus epilepsy is TBC1D24 (TBC 1 domain family member 24), TBC1D24 encodes a protein with a conserved domain, termed the TBC domain, which is characteristic of a protein that interacts with gtpase, the TBC domain proteins being the gtpase activator protein of a specific group gtpase, these gtpase being Rab (intra-brain ras related protein) small gtpase involved in regulating membrane transport, TBC domain abnormalities associated with myoclonus epilepsy, which is induced when a specific group of gtpase activator proteins of gtpase are abnormal, mucha BE et al (PMID: 25719194) also report TBC1D 24-related diseases including familial infantile myoclonus epilepsy. In addition, in a wide field of genetics, complex heterozygous mutation is a unique phenomenon, and is also called double allelic mutation, each chromosome is mutated and is not a wild chromosome, but the types of alleles generated by mutation of two chromosomes are different. The compound heterozygous mutation is that two different mutations are generated on the same gene, wherein the two mutations are respectively from a mother and a father, and both the two mutations can influence the functions of the protein encoded by the gene. This is often observed in genetic disease because one mutation is often insufficient to cause a significant genetic disease, but when two mutations are present at the same time they may interact, resulting in the occurrence of the disease. At present, the research on the connection between the diseases and the specific genes is still to be deeply researched, the screening means for the diseases is still to be perfected, the early screening of the potential easily-occurring diseases is realized, and a new idea is provided for subsequent treatment and early intervention. Disclosure of Invention The invention provides a gene mutant and application thereof, which mainly aims to solve the problems that the pathogenic gene library of the type 1 of the autosomal dominant acoustic neuropathy of the familial infant myoclonus epilepsy is imperfect in the screening and diagnosis process, part of potential risks of morbidity cannot be screened, the treatment means for the symptoms are still to be perfected, and the like. In order to solve the problems, the invention adopts the following technical scheme: the invention relates to a TBC1D24 gene mutant and application thereof. One of them is any one of the following TBC1D24 gene mutants, and any one is satisfied and is within the scope of the present invention: A nucleic acid TBC1D24-1 having a fragment of interest therein, said fragment of interest having a mutation of c.677_680delCCCG as compared to the wild-type TBC1D24 gene having the sequence of SEQ ID NO. 1; a nucleic acid TBC1D24-2 having a fragment of interest therein and having a c.731C > T mutation compared to the wild-type TBC1D24 gene having the sequence of SEQ ID NO. 1; A polypeptide TBC1D24-1 having a p.a226gfs×28 mutation compared to the protein encoded by the wild-type TBC1D24 gene having the sequence SEQ ID No. 2; The polypeptide TBC1D24-2 has a p.A244V mutation as compared to the protein encoded by the wild-type TBC1D24 gene having the sequence SEQ ID NO. 2. Wherein, one of the other cases is that the TBC1D24 gene composite mutant comprises composite heterozygous mutation, and the composite heterozygous mutation comprises both the c.677_680delCCCG mutation and the c.731C > T mutation, or, And in the other case, the TBC1D24 gene mutant is a TBC1D24 composite mutant protein encoded by a TBC1D24 gene complex, and the TBC1D24 composite mutant protein simultaneously has p.A226Gfs 28 mutation and p.A244V mutation. The second application of the reagent which is the TBC1D24 gene mutant in preparing a product for screening family infant myoclonus epilepsy at least comprises the following cases: 1) When the product for scre