Application of C7orf10 protein level detection agent in preparation of mitochondrial disease diagnostic agent

Abstract

The invention relates to application of a C7orf10 protein level detection agent in preparation of a mitochondrial disease diagnostic agent. Research finds that C7orf10 protein level rise is shown in cells with mitochondrial dysfunction caused by different gene defects and in the body of a patient, which indicates that the C7orf10 protein level rise can be used as a molecular marker of the mitochondrial dysfunction, so that a C7orf10 protein level detection agent can be used as a mitochondrial disease diagnosis agent, and the clinical application prospect is wide. Therefore, a novel diagnosis method and a novel diagnosis reagent are provided for diagnosis of mitochondrial diseases.

Description

Technical Field

[0001] The present invention belongs to the field of mitochondrial disease diagnosis, and more particularly, relates to the use of a C7orf10 protein level detection agent in the preparation of a mitochondrial disease diagnostic agent. Background Art

[0002] Mitochondrial diseases are multisystem, complex disorders that are difficult to diagnose. They are caused by pathogenic variants in at least 350 different genes in the 2 genomes, and this list continues to grow as more disease genes are frequently discovered.

[0003] The difficulty in diagnosing mitochondrial diseases lies in the great uncertainty in the symptoms and age of onset of the disease, as well as the lack of consistent biochemical markers. In addition, many clinical symptoms of mitochondrial diseases, such as muscle hypotonia and weakness, intestinal dysmotility, and neurological dysfunction, are shared by a variety of other disease processes and therefore cannot be used to identify mitochondrial diseases. Similarly, some blood biochemical markers (such as elevated lactate and alanine) help to improve the diagnosis of mitochondrial diseases, but abnormalities in these markers do not completely correlate with abnormal mitochondrial function, and these markers may appear normal in some individuals with mitochondrial diseases.

[0004] Therefore, there is a need to develop new molecular markers for the diagnosis of mitochondrial diseases. Summary of the invention

[0005] In order to solve the above problems, the present invention provides the use of a C7orf10 protein level detection agent in the preparation of a mitochondrial disease diagnostic agent.

[0006] In a specific embodiment, the C7orf10 protein sequence is shown as SEQ ID NO:1.

[0007] In a specific embodiment, the mitochondrial disease is selected from mitochondrial diseases caused by one or more combinations of the following gene defects in mitochondria: MTO1 defect, ETHE1 defect, PET100 defect, ATP6 defect, MRPS22 defect.

[0008] The present invention also provides a diagnostic agent for mitochondrial diseases, comprising a C7orf10 protein level detection agent.

[0009] In a specific embodiment, the C7orf10 protein sequence is as shown in SEQ ID NO:1.

[0010] In a specific embodiment, the C7orf10 protein level detection agent is a specific antibody against C7orf10.

[0011] The present invention has found through research that elevated levels of C7orf10 protein are present in cells and patients with mitochondrial dysfunction caused by different gene defects, indicating that elevated levels of C7orf10 protein can be used as a molecular marker for mitochondrial dysfunction. Therefore, a C7orf10 protein level detector can be used as a mitochondrial disease diagnostic agent, thereby providing a new diagnostic method and diagnostic reagent for the diagnosis of mitochondrial diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 Immunoblotting photographs to detect C7orf10 protein levels in Hek293 and U20S cells in which the mitochondrial genes Eral1, Rbfa or mtRF1 were knocked out.

[0013] Figure 2 The following are photos of immunoblotting to detect the level of C7orf10 protein in primary fibroblast cell lines from patients with mitochondrial diseases. DC is a primary fibroblast cell line from a healthy person; MTO1 / IM is a primary fibroblast cell line from a patient with mitochondrial MTO1 deficiency; ETHE1 / IM is a primary fibroblast cell line from a patient with mitochondrial ETHE1 deficiency. Normalized C7 level: Fold change of C7orf10 protein expression relative to DC in the control group.

[0014] Figure 3 The following are photos of immunoblotting to detect the level of C7orf10 protein in primary fibroblast cell lines from patients with mitochondrial diseases. Among them, DC is a primary fibroblast cell line from healthy people; C_AR is a primary fibroblast cell line from healthy people; PET100: a primary fibroblast cell line from a patient with mitochondrial PET100 deficiency; ATP6 is a primary fibroblast cell line from a patient with mitochondrial ATP6 deficiency; MRPS22 is a primary fibroblast cell line from a patient with mitochondrial MRPS22 deficiency. Normalized C7 level: the fold change of C7orf10 protein expression relative to that of DC in the control group DETAILED DESCRIPTION

[0015] The principles and features of the present invention are described below in conjunction with the accompanying drawings. The examples given are only used to explain the present invention and are not used to limit the scope of the present invention.

[0016] 1. Increased levels of C7orf10 protein in cells due to specific mitochondrial gene defects

[0017] The genes Eral1, Rbfa or mtRF1 were knocked out in Hek293 and U20S cells, respectively, and the changes in the levels of some proteins in the mutants were detected.

[0018] The results are as follows Figure 1 As shown in Figure 1, after knocking out the three genes respectively, the expression of C7orf10 protein increased significantly. It is speculated that mitochondrial dysfunction may lead to increased levels of C7orf10 protein in cells. The amino acid sequence of the protein is shown in SEQ ID NO: 1.

[0019] 2. C7orf10 protein levels are elevated in primary fibroblast cell lines from patients with mitochondrial disease

[0020] The levels of C7orf10 protein were detected in fibroblast cell lines from healthy individuals and fibroblast cell lines from patients with different mitochondrial gene defects. Figure 2 and 3 As shown, the primary fibroblast cell lines of patients with mitochondrial MTO1 deficiency, mitochondrial ETHE1 deficiency, mitochondrial PET100 deficiency, mitochondrial ATP6 deficiency, and mitochondrial MRPS22 deficiency all showed significantly elevated C7orf10 protein levels relative to those of healthy controls.

[0021] These experiments show that the levels of C7orf10 protein are increased in patients with different mitochondrial gene defects, suggesting that elevated levels of C7orf10 protein can be used as a marker of mitochondrial dysfunction, indicating that the subject suffers from mitochondrial disease.

[0022] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. Application of C7orf10 protein level detection agent in the preparation of mitochondrial disease diagnostic agent.

2. The use according to claim 1, characterized in that: The C7orf10 protein sequence is shown in SEQ ID NO:

1.

3. The use according to claim 1, characterized in that: The mitochondrial disease is selected from mitochondrial diseases caused by one or more combinations of the following gene defects in mitochondria: MTO1 defect, ETHE1 defect, PET100 defect, ATP6 defect, MRPS22 defect.

4. A diagnostic agent for mitochondrial diseases, characterized in that: Includes a C7orf10 protein level detection reagent.

5. The diagnostic agent for mitochondrial diseases according to claim 4, characterized in that The C7orf10 protein sequence is shown in SEQ ID NO:

1.

6. The diagnostic agent for mitochondrial diseases according to claim 4, characterized in that The C7orf10 protein level detection agent is a specific antibody against C7orf10.

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