Novel pathogenic variants in <scp>NLRP7</scp>, <scp>NLRP5,</scp> and <scp>PADI6</scp> in patients with recurrent hydatidiform moles and reproductive failure

Rezaei, Maryam; Suresh, Beena; Bereke, Eric; Hadipour, Zahra; Aguinaga, Mónica; Qian, Jun; Bagga, Rashmi; Fardaei, Majid; Hemida, Reda; Jagadeesh, Sujatha; Majewski, Jacek; Slim, Rima

doi:10.1111/cge.13941

Cited by 25 publications

(8 citation statements)

References 9 publications

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“…During oogenesis, PADI6 functions by catalyzing the deamination of arginine residues in proteins, potentially contributing to cytoskeletal reorganization in oocytes and preimplantation embryos. Studies on Padi6 -deficient mice have shown that these animals are infertile due to developmental defects in preimplantation embryos, highlighting the crucial role of PADI6 in female fertility ( Rezaei et al, 2021 ). Furthermore, previous research has linked PADI6 to other reproductive deficiencies, strengthening the association between PADI6 and infertility, miscarriages, and molar pregnancies ( Qian et al, 2018 ; Maddirevula et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Padi6 expression patterns in buffalo oocytes and preimplantation embryos

Sun,

Yang,

Zhang

et al. 2024

Anim. Reprod.

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The subcortical maternal complex, which consists of maternal-effect genes, plays a crucial role in the development of oocytes and preimplantation embryo until the activation of the zygote genome. One such gene, known as peptidyl-arginine deiminase VI ( Padi6 ), is involved in the oocyte maturation, fertilization and embryonic development. However, the precise function of Padi6 gene in buffalo is still unclear and requires further investigation. In this study, the sequence, mRNA and protein expression patterns of Padi6 gene were analyzed in oocytes, preimplantation embryos and somatic tissues of buffalo. The coding sequence of gene was successfully cloned and characterized. Real-time quantitative PCR results indicated an absence of Padi6 transcripts in somatic tissues. Notably, the expression levels of Padi6 in oocytes showed an increased from the germinal vesicle stage to metaphase II stage, followed by a rapid decrease during the morula and blastocyst stages. Immunofluorescence analysis confirmed these findings, revealing a noticeable decline in protein expression levels. Our research provides the initial comprehensive expression profile of Padi6 in buffalo oocytes and preimplantation embryos, serving as a solid foundation for further investigations into the functionality of maternal-effect genes in buffalo.

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Section: Discussionmentioning

confidence: 99%

Padi6 expression patterns in buffalo oocytes and preimplantation embryos

Sun,

Yang,

Zhang

et al. 2024

Anim. Reprod.

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“…The other patient, with a homozygous mutation producing I599N PADI6, had a total of seven pregnancies that ended with three miscarriages and the formation of four HMs. Two of these molar pregnancies reached as late as 15 and 32 weeks gestation [19]. The extended duration and altered phenotype of these pregnancies have been attributed to the differences in mutation severity, specifically the effects of missense mutations versus premature truncations.…”

Section: (A) Padi6 Mutations In Womenmentioning

confidence: 99%

“…Of the PADI family, PADI6 was the last to be identified and is the least well-characterized. Predominantly expressed in the oocyte and early embryo, PADI6 is crucial for early embryonic development and female fertility in both humans and mice [7,[11][12][13][14][15][16][17][18][19][20][21][22][23][24]. However, the molecular mechanisms responsible for this role are unclear, and notably there is currently no reported catalytic activity of PADI6.…”

Section: Introductionmentioning

confidence: 99%

PADI6: What we know about the elusive fifth member of the peptidyl arginine deiminase family

Williams,

Walport

2023

Phil. Trans. R. Soc. B

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Peptidyl arginine deiminase 6 (PADI6) is a maternal factor that is vital for early embryonic development. Deletion and mutations of its encoding gene in female mice or women lead to early embryonic developmental arrest, female infertility, maternal imprinting defects and hyperproliferation of the trophoblast. PADI6 is the fifth and least well-characterized member of the peptidyl arginine deiminases (PADIs), which catalyse the post-translational conversion of arginine to citrulline. It is less conserved than the other PADIs, and currently has no reported catalytic activity. While there are many suggested functions of PADI6 in the early mouse embryo, including in embryonic genome activation, cytoplasmic lattice formation, maternal mRNA and ribosome regulation, and organelle distribution, the molecular mechanisms of its function remain unknown. In this review, we discuss what is known about the function of PADI6 and highlight key outstanding questions that must be answered if we are to understand the crucial role it plays in early embryo development and female fertility. This article is part of the Theo Murphy meeting issue ‘The virtues and vices of protein citrullination’.

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“…Second, PADI6 is one of the genes encoding the subcortical maternal complex (SCMC), which is necessary for oocyte maturation and early embryonic development. Therefore, the loss and mutation of PADI6 destabilizes SCMC, resulting in abnormal oocyte maturation, fertilization failure, early embryonic developmental arrest, multilocus imprinting disorder, molar pregnancy, miscarriage, and female infertility (32,(190)(191)(192)(193)(194)(195)(196)(197)(198)(199)(200)(201)(202)(203)(204)(205)(206)(207).…”

Section: The Padi Family and Reproductive Development-related Diseasesmentioning

confidence: 99%

Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review

2023

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The peptidyl arginine deiminase (PADI) family is a calcium ion-dependent group of isozymes with sequence similarity that catalyze the citrullination of proteins. Histones can serve as the target substrate of PADI family isozymes, and therefore, the PADI family is involved in NETosis and the secretion of inflammatory cytokines. Thus, the PADI family is associated with the development of inflammatory autoimmune diseases and cancer, reproductive development, and other related diseases. In this review, we systematically discuss the role of the PADI family in the pathogenesis of various diseases based on studies from the past decade to provide a reference for future research.

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Novel pathogenic variants in NLRP7, NLRP5, and PADI6 in patients with recurrent hydatidiform moles and reproductive failure

Cited by 25 publications

References 9 publications

Padi6 expression patterns in buffalo oocytes and preimplantation embryos

Padi6 expression patterns in buffalo oocytes and preimplantation embryos

PADI6: What we know about the elusive fifth member of the peptidyl arginine deiminase family

Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review

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