Abstract
Purpose
Oocyte death is a severe clinical phenotype that causes female infertility and recurrent in vitro fertilization and intracytoplasmic sperm injection failure. We aimed to identify pathogenic variants in a female infertility patient with oocyte death phenotype.
Methods
Sanger sequencing was performed to screen PANX1 variants in the affected patient. Western blot analysis was used to check the effect of the variant on PANX1 glycosylation pattern in vitro.
Results
We identified a novel PANX1 variant (NM_015368.4 c.86G > A, (p. Arg29Gln)) associated with the phenotype of oocyte death in a non-consanguineous family. This variant displayed an autosomal dominant inheritance pattern with reduced penetrance. Western blot analysis confirmed that the missense mutation of PANX1 (c.86G > A) altered the glycosylation pattern in HeLa cells. Moreover, the mutation effects on the function of PANX1 were weaker than recently reported variants.
Conclusion
Our findings expand the inheritance pattern of PANX1 variants to an autosomal dominant mode with reduced penetrance and enrich the variational spectrum of PANX1. These results help us to better understand the genetic basis of female infertility with oocyte death.
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Data availability
All data generated and analyzed in this study are included in this published manuscript.
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Acknowledgements
We sincerely thank the patient and her family for their participation and support in this study.
Funding
This work was supported by the National Natural Science Foundation of China (81960271 and 81960288), the Major Research and Development Project of Science and Technology Department of Jiangxi Province (20203BBGL73140), and the JXHC Key Laboratory of Fertility Preservation.
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JT, QW, and ZL conceived and designed the study. DX, ZZ, CX, and ZH contributed to the recruitment, characterization, and oocyte image of the patient. PL, LC, and LF performed the exon sequencing. PL performed the cell culture, expression vector transfection, and western blot. And LX and JH organized the medical records. XW, JC, and YZ contributed to the bioinformatics analysis. XW and JT wrote the draft of the manuscript. All the authors commented on previous version of the manuscript and approved the final manuscript.
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This study was conducted in accordance with the guidelines of the Declaration of Helsinki and was approved by the Clinical Ethical Committee of Jiangxi Maternal and Child Health Hospital, and informed consents from patient were obtained before the initiation of the study. All the authors consented to participate in this study.
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Wu, XW., Liu, PP., Zou, Y. et al. A novel heterozygous variant in PANX1 is associated with oocyte death and female infertility. J Assist Reprod Genet 39, 1901–1908 (2022). https://doi.org/10.1007/s10815-022-02566-1
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DOI: https://doi.org/10.1007/s10815-022-02566-1