{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:46:31Z","timestamp":1785797191367,"version":"3.56.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      TANGO2 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\n                      <jats:italic>TANGO2<\/jats:italic>\n                      gene (NM_152906.7).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In 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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Whole-exome sequencing revealed that the proband was a compound heterozygote with c.672C&amp;gt;A (p.Y224*) and an exon 5-6 deletion (c.266_451del (p.E89Tfs\n                      <jats:sup>*<\/jats:sup>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Taken 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1832329","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:10:20Z","timestamp":1785795020000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["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"],"prefix":"10.3389","volume":"17","author":[{"given":"Wanna","family":"Ke","sequence":"first","affiliation":[{"name":"Reproductive Medicine Center, Boai Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Wen","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Boai Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanhui","family":"Ou","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Boai Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowu","family":"Fang","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Boai Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junye","family":"Huo","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Boai Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufeng","family":"Lin","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Boai Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xubin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Boai Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiming","family":"Li","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Boai Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1002\/jimd.12579","article-title":"Vitamin B5, a coenzyme A precursor, rescues TANGO2 deficiency disease-associated defects in drosophila and human cells","volume":"46","author":"Asadi","year":"2023","journal-title":"J. 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