Preimplantation Genetic Testing for Aicardi–Goutières Syndrome Induced by Novel Compound Heterozygous Mutations of TREX1: an unaffected Live Birth

Abstract

Abstract Background: Aicardi–Goutières syndrome (AGS) is a rare, autosomal recessive, hereditary neurodegenerative disorder. Which is characterized mainly by early onset progressive encephalopathy, concomitant with an increase in interferon-α levels in the cerebrospinal fluid. Preimplantation genetic testing (PGT) is a procedure that could choose unaffected embryos to transferr after analysis of biopsied cells, which allows at-risk couples without facing the risk of pregnancy termination. Methods: Trio-WES, Karyotype and chromosomal microarray analysis (CMA) were used for determining the family’s pathogenic mutations. To blocked the inheritance of the disease, multiple annealing and looping-based amplification cycles (MALBAC) was used for whole genome amplification of biopsied trophectoderm(TE) cells. Sanger sequencing and single nucleotide polymorphism (SNP) haplotyping were used to detect the state of gene mutations. Copy number variations (CNV) analysis was also carried out to prevent embryonic chromosomal abnormalities. Prenatal diagnosis was preformed to verify the PGT outcomes. Results: A total of 3 blastocysts formed after intracytoplasmic sperm injection were biopsied. After genetic analysis, an embyro identified heterozygous mutation in TREX1 without CNVs was transferred. The couple finally got a healthy baby through PGT with haplotype linkage analysis. Conclusions: In this study, we first identified two noval pathogenic mutations in TREX1, which has not been previously reported. Our study provided valuable knowledge of the molecular diagnosis and genetic counseling for AGS and extends the mutation spectrum of TREX1 gene.