Background: Early embryonic developmental stagnation is one of the reasons that affect the outcome of in vitro fertilization-embryo transfer, leading to the depletion of available embryos or failure after transplantation. It has been shown that defects in the ribonucleotide-reductase lead to cell cycle arrest, developmental delay, and high mutation rates.
Case presentation: Two female patients, who were siblings from an inbreeding family, suffered primary infertility of unknown causes and early embryonic developmental arrest during IVF treatment. A total of 39 oocytes were obtained from the patients in collectively 5 IVF/ICSI cycles, of which 37 were mature eggs, only 2 transplantable embryos were formed, and no pregnancy was achieved. Whole genome sequencing and Sanger sequencing were adopted to identify and confirm variations that might cause early embryo developmental stagnation in this family. We identified a homozygous variant c.262C>T:p.His88Tyr in ribonucleotide-diphosphate reductase subunit M2 (RRM2) in both patients and their parents each carried a heterozygous allele. Pedigree analysis showed an autosomal recessive inheritance pattern. Function of this variant was predicted by online databases, which indicated it to be a potential pathogenic mutation.
Conclusions: We identified RRM2 as a potential causative gene for early embryonic developmental stagnation. It was also suggested that RRM2 might be a maternal effect gene.
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Posted 30 Jul, 2020
Posted 30 Jul, 2020
Background: Early embryonic developmental stagnation is one of the reasons that affect the outcome of in vitro fertilization-embryo transfer, leading to the depletion of available embryos or failure after transplantation. It has been shown that defects in the ribonucleotide-reductase lead to cell cycle arrest, developmental delay, and high mutation rates.
Case presentation: Two female patients, who were siblings from an inbreeding family, suffered primary infertility of unknown causes and early embryonic developmental arrest during IVF treatment. A total of 39 oocytes were obtained from the patients in collectively 5 IVF/ICSI cycles, of which 37 were mature eggs, only 2 transplantable embryos were formed, and no pregnancy was achieved. Whole genome sequencing and Sanger sequencing were adopted to identify and confirm variations that might cause early embryo developmental stagnation in this family. We identified a homozygous variant c.262C>T:p.His88Tyr in ribonucleotide-diphosphate reductase subunit M2 (RRM2) in both patients and their parents each carried a heterozygous allele. Pedigree analysis showed an autosomal recessive inheritance pattern. Function of this variant was predicted by online databases, which indicated it to be a potential pathogenic mutation.
Conclusions: We identified RRM2 as a potential causative gene for early embryonic developmental stagnation. It was also suggested that RRM2 might be a maternal effect gene.
Figure 1
Figure 2
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