A pathogenic mutation of hereditary gametogenesis disorder and its detection reagent

The technology of a reagent and a kit is applied in the field of the pathogenic mutation of hereditary male and female gametogenesis disorder and its detection reagent, which can solve the problems such as unreported

CN112226439BActive Publication Date: 2021-09-03NANJING MATERNITY & CHILD HEALTH CARE HOSPITAL
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Publication Date
2021-09-03

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Abstract

The invention discloses a pathogenic mutation of hereditary gametogenesis disorder and a detection reagent thereof. A mutated Pof1b gene, the mutated Pof1b gene is located on chromosome X, is a deletion mutation c.312_316delp.S104fs, and the gene number of the wild-type Pof1b gene in the Ensemble database is: ENSG00000124429, where the Pof1b gene of the deletion mutation is physically The position is the third exon, the chrX-84622737-84622742 base is missing five bases TACAT, and the subsequent sequence causes a frameshift mutation. The mutated Pof1b gene or the mutated POF1B protein is used as a detection target in the preparation of auxiliary diagnostic reagents or detection equipment for male non-obstructive azoospermia or female hereditary primary ovarian insufficiency.
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Description

technical field

[0001] The invention belongs to the field of biomedicine and relates to a pathogenic mutation of hereditary male and female gametogenesis disorder and a detection reagent thereof. Background technique

[0002] Primary ovarian insufficiency (POI) refers to amenorrhea in women before the age of 40, accompanied by increased gonadotropin levels and decreased estrogen levels, and a certain degree of perimenopause caused by a series of low estrogen levels. Symptoms such as hot flashes, hyperhidrosis, facial flushing, low libido, mood changes, etc. About 1-2% of women of childbearing age suffer from this disease. According to the development process of the disease, primary ovarian insufficiency is divided into three development stages: occult stage, biochemical abnormal stage, and clinical failure stage. Premature ovarian failure (POF) is the terminal stage. POF means that there are very few eggs that can develop and ovulate, and there is still no effective way to ...

Examples

Embodiment 1

[0045] To detect the Pof1b gene mutation in a family with hereditary primary ovarian insufficiency and azoospermia.

[0046] experimental method:

[0047] 1. Collection of clinical resources of the family and establishment of a genetic resource bank:

[0048] The clinical data of each member of the family and blood samples of two patients (III:6, III:8) and their parents were collected. The proband in this family is patient III:8, male, who was diagnosed with non-obstructive azoospermia in our hospital two years ago; his brother has normal fertility; his sister (III:6) has hereditary primary ovarian Insufficient, its parents are not consanguineous. (Family diagram see figure 1 ). Clinical data mainly include personal medical history, family history, birth history, etc. Genomic DNA was extracted from the blood of two patients (III:6, III:8) and their parents with a blood genomic DNA extraction kit (Qiagen, Hilden, Germany).

[0049] 2. Discover the pathogenic mutations in...

Embodiment 2

[0077] Biological analysis was performed on the pathogenic mutations Pof1b c.312_316del p.S104fs and Pof1bc.1325A>G p.E442G detected in Example 1.

[0078] experimental method:

[0079] 1. Conservative analysis:

[0080] The NCBI HomoloGene database (http: / / www.ncbi.nlm.nih.gov / homologene) was used to evaluate and predict the conservation of the screened mutations in multiple species. The change point is conserved in the evolution process, which confirms that the mutation of the change point may cause more serious pathological diseases. The results are shown in Figure 7 .

[0081] 2. Research on protein crystal structure changes:

[0082] SWISS MODEL (http: / / swissmodel.expasy.org / ) prediction software was used to predict the structure of the POF1B wild-type protein and the mutant protein carrying the p.S104fs mutation, and evaluate the protein structure changes caused by the mutation. The prediction results of the protein crystal structure showed that the c.312_316del p.S...