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Preimplantation Genetic Testing for Rare Inherited Disease of MMA-CblC: an Unaffected Live Birth

  • Reproductive Genetics: Case Study
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Methylmalonic acidemia combined with homocysteinemia and cobalamin C type (MMA-CblC, MIM # 277400) is a rare inherited disease with cobalamin metabolic disorder, which are caused by deficiency in the MMACHC gene. A couple with a proband child carried with compound heterozygous mutations of MMACHC (c.609G>A and c.567 dup T, NM_015506) sought for assisted reproductive technology to avoid the transmission of pathogenic genetic variants and unnecessary induction of labor. Thus, in vitro fertilization (IVF), preimplantation genetic testing (PGT), and prenatal genetic diagnosis were applied to fulfill this clinical demand. In this study, seven embryos were biopsied and carried out whole-genome amplification using multiple annealing and looping-based amplification cycle (MALBAC) method. Sanger sequencing together with copy number variation (CNV) analysis and single-nucleotide polymorphism (SNP) haplotyping was conducted to detect the mutated alleles and chromosomal abnormalities simultaneously. Three embryos (E07, E06, and E02) were confirmed without CNVs and inherited mutations at MMACHC gene. Embryo E07 with the best embryo ranking of 5BB was selected preferentially to transfer which led to a successful pregnancy and an unaffected live birth. Prenatal genetic diagnosing with amniotic fluid cells, Sanger sequencing with cord blood cells, and neonate MMA screening further verified our successful application of PGT in preventing mutated allele transmission for this rare inherited disease.

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We thank the family for their cooperation and participation. We thank the embryology team at the Center of Reproductive Medicine for the help with sample preparation. We also thank Zhen liu and Jian Wu from Yikon Genomics for the technical help for data analysis.

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Correspondence to Xinlian Chen or Shanling Liu.

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The present study was approved by the Ethics Committee of West China Second Hospital of Sichuan University. All patients provided written informed consent.

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The authors declare no competing interests.

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Table S1

SNP haplotyping linkage analysis for the pedigree and embryo samples (DOCX 23 kb)


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Peng, C., Ren, J., Li, Y. et al. Preimplantation Genetic Testing for Rare Inherited Disease of MMA-CblC: an Unaffected Live Birth. Reprod. Sci. 28, 3571–3578 (2021).

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