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The discovery of a new genetic disease called "germ cell death"

04-09 BigMediumSmall I want to comment


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Recently, Science Translational Medicine, a journal of Science magazine, published the latest research results of Kuang Yanping team from the Department of Assisted Reproduction, Ninth People's Hospital Affiliated to Medical College of Shanghai Jiaotong University, in conjunction with Sang Qing and Wang Lei team of Fudan University. This study revealed that the mutation of PANX1, a member of the connexin family, was pathogenic, and clarified its pathogenic mechanism. It also provided the first mouse model to study the pathological function of PANX1 in depth. The study lasted 15 years. A new Mendelian hereditary disease, fertilized egg death, was discovered and named.

PANX1 is a member of the Pannnexin (PANX) family. Previous studies have reported that PANX1 is related to inflammation, infection, ischemia and other physiological and pathological processes, but there is no obvious abnormality in PANX1 knockout mice. These evidences seem to indicate that PANX1 is not important. In 2003, Professor Kuang Yanping found a peculiar case in the clinical practice of IVF technology: the number of eggs taken from patients, the shape of eggs and in vitro fertilization were normal, but after the second day of egg fertilization, all embryos appeared blackening, atrophy and degeneration. Subsequently, he found a familial patient with similar phenotype, and a sporadic patient with more severe phenotype: after the eggs were taken out, the unfertilized eggs showed blackening, atrophy and degeneration. In 2015, Kuang Yanping team joined Sang Qing and Wang Lei team to carry out research. Meanwhile, Professor Shi Juanzi of the Reproductive Center of Northwest Women's and Children's Hospital also found a similar case of familial patients. At that time, the team named the disease "egg death". Through more than three years of joint research, the team found different mutations in PANX1, a member of the connexin family, in four independent families, and revealed the pathogenic mechanism through cell level, Xenopus laevis oocyte, mouse model and other perspectives: mutations caused phenotype by affecting protein glycosylation, activating channels, accelerating ATP release. This disease accords with Mendelian dominant inheritance, which proves that egg death is a new Mendelian inheritance disease.

PANX1 is a glycosylated protein. Subsequent functional experiments on cells and eggs showed that the mutation would change the glycosylation pattern of PANX1, suggesting that egg death is also a new glycosylation disease.

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