The new human genetic disease "egg death" has been discovered and named

new Mendel genetic disease, glyco-based disease and ion channel disease - "egg death" was discovered and named by Chinese scientists.
The team at the Ninth People's Hospital, affiliated with Shanghai Jiaoda University School of Medicine, and the team of Sang Qing and Wang Lei of Fudan University revealed the mechanism of PANX1 mutation pathogenicity, and provided the first mouse model to study PANX1 pathology in depth.
the study was published March 28 in the journal Science Translational Medicine.according to
, the researchers took 15 years, in four independent families, found that cell-connected protein family members PANX1 there are different mutations, and through cell levels, claw eggs, mouse models and other angles to reveal the pathogenic mechanism: mutations by affecting protein glycosylation, activation channels, acceleration of ATP release, ideotype appearance, thus proving that egg death is a brand-new Mendel genetic disease and glycosylation disease, is also the first abnormal ion disease of PANX family members.
and communication between cells is necessary for biological organisms to maintain normal physiological function. The Connexin and Pannexin families are important ion channels that form connections between cells, and the signaling pathways they control play a key role in the normal physiological role of cells. The Connexin (Cx) family consists of 21 members, some of whom have been found to cause a number of diseases.
Pannnexin (PANX) family consists of three members PANX1, 2, 3. To date, no disease has been detected as a result of the mutation of the three members. PANX1 was cloned in 2003, and over the next 10 years, numerous studies reported that it was related to physiological pathological processes such as inflammation, infection, and local isoemia, but there were no obvious abnormalities in PANX1 knock-out mice: rats were bred, and there were no abnormalities in other organs. The evidence seems to suggest that PANX1 is not important.
In 2003, Professor Yanping Yanping discovered a strange case in clinical IVF: the number of eggs taken by patients, the shape of the eggs and in-body fertilization were normal, but after the second day of fertilization, all embryos were blackened, atrophy and degenerated. Subsequently, a familial patient with a similar esoptype (family 2) and a patient with a more severe esop lineage were found: after the egg was removed, the unseated was shown to be blackened, atrophy, and degenerative (family 3). At that time, no medical literature reported the disease, and no one described the cause and mechanism of the disease is unknown.
2015, Yanping and Sang Qing and Wang Lei began to carry out research. During this period, a similar case of familial patient (family division 1) was also found by Professor Shi Zi of the Reproductive Center of Northwest Women's and Children's Hospital. At the time, the team named the disease "egg death."
more than three years of joint research, researchers found different mutations in PANX1 in four separate family systems, a disease that conforms to Mendel's explicit genetic characteristics and identifies "egg death" as a new Typel genetic disease.
PANX1 is a glycosylated protein, and subsequent series of functional experiments on cells and eggs have shown that mutations alter panx1's glycosylation pattern, which is closely related to disease, indicating that egg death is also a new glycosylation disease.
study of eggs and claw eggs in in-body mice showed that mutations caused abnormal activation of panx1 channels, which accelerated the release of ATP inside the egg, leading to disease. In the experiment, the fertility of the four PANX1-point mutant mice was normal and no apparent esophotype, while PANX1's expression in human eggs was significantly higher than that of rat eggs, which the researchers speculated may be the cause of the mutant mice's esopolyticity. The wild and mutant PANX1 over-expression mouse models specifically expressed in the egg were further developed. The mutant mouse model shows infertility and accurately simulates the esophoo of egg death.
experts believe the study expands understanding of mendelian disease in humans, reveals a large number of previously unknown new genes hidden in human eggs and early embryonic development, and lays the foundation for genetic counseling and precision medicine practices in assisted reproduction in related patients.
, Sang Qing Associate Researcher, Professor Yanping Yanping and Professor Wang Lei are the authors of the paper's newsletter. Zhang Zhihua, Ph.D., Fudan Institute of Biomedical Research, Professor Shi Zizi of Northwest Women's and Children's Hospital, Professor Sun Xiaoxi of Fudan University's Affiliated Obstetrics and Gynecology Hospital, and Dr. Li Bin and Dr. Yu, Department of Assisted Reproduction, Shanghai Jiuyuan, are co-authors. Researcher Sun Qiang, a member of the team at the Institute of Neurology of the Chinese Academy of Sciences, also participated in the study. (Source: Science Network Huang Xin Xuying)
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