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Preimplantation genetic testing and prenatal diagnosis of TANGO2 deficiency disorder with biallelic pathogenic variants using single-nucleotide polymorphism-based haplotyping and gap-polymerase chain reaction
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DOI：10.3389/fgene.2026.1832329.png)
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Abstract
En 中文
IntroductionTANGO2 deficiency disorder (TDD); characterized by developmental delays; intellectual disability; gait incoordination; speech difficulties; seizures; and hypothyroidism; is a rare genetic disease caused by biallelic pathogenic variants of the TANGO2 gene (NM_152906.7).MethodsIn this study; we aimed to present a comprehensive approach for the management of TDD through preimplantation genetic diagnosis and subsequent prenatal diagnosis using single-nucleotide polymorphism (SNP)-based haplotyping and gap-polymerase chain reaction (PCR).ResultsWhole-exome sequencing revealed that the proband was a compound heterozygote with c.672C>A (p.Y224*) and an exon 5-6 deletion (c.266_451del (p.E89Tfs*124)). We confirmed these two pathogenic variants using Sanger sequencing and quantitative PCR copy number variation (CNV) analysis; respectively. We successfully constructed an SNP-based haplotype using next-generation sequencing (NGS) in the preclinical phase of preimplantation genetic testing (PGT). In the clinical phase of embryo diagnosis; embryos were subjected to PGT; including NGS-based SNP haplotype linkage and chromosomal CNV analyses. Notably; we successfully identified the exact breakpoints of exon 5-6 deletion (NC_000022.11:g.20053363_20057022delinsAGGT; GRCh38/hg38) using long-range PCR and designed a gap-PCR system based on the location of the breakpoints for subsequent prenatal diagnosis.DiscussionTaken together; our study provides a method for PGT and subsequent prenatal diagnosis of TDD using SNP-based haplotyping and gap-PCR. The two novel pathogenic variants identified in this study extend the mutational spectrum of TDD.
Keywords:
preimplantation genetic testing
prenatal diagnosis
TANGO2 deficiency disorder
breakpoints
gap-PCR
SNP-based haplotype
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