{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T22:58:35Z","timestamp":1780959515044,"version":"3.54.1"},"reference-count":11,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"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>Objective<\/jats:title>\n                    <jats:p>Premature ovarian insufficiency (POI) with short stature and mild intellectual disability can have diverse genetic etiologies. We aimed to decipher the genetic basis of this complex phenotype in a 26-year-old female with a karyotype lacking aneuploidy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and Methods<\/jats:title>\n                    <jats:p>This is a case study integrated with comprehensive genetic analyses. After standard techniques (karyotyping, CNV-seq, WES) failed to yield a diagnosis, Oxford Nanopore long-read sequencing was employed to map chromosomal breakpoints at single-base resolution. X-inactivation (XCI) analysis was also performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Long-read sequencing refined the karyotype to 46,X,t(X; 3;8) (q25; q21p21; p21),t(17; 22)(q21.2; q13) and identified direct disruptions of TAFA5, LARS2, and MYLK. XCI analysis demonstrated highly skewed XCI (5.35%), indicating preferential inactivation of the structurally normal X chromosome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We propose that highly skewed XCI is the primary driver of the patient\u2019s POI and short stature, while the three disrupted genes may serve as modifying factors. This study underscores the value of long-read sequencing in resolving CCRs and the importance of XCI analysis in female patients with X-chromosome rearrangements.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1811784","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T22:10:20Z","timestamp":1780956620000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Deciphering a de novo complex chromosomal rearrangement causing premature ovarian insufficiency, short stature, and mild intellectual disability using long-read sequencing"],"prefix":"10.3389","volume":"17","author":[{"given":"Qingqiu","family":"Cheng","sequence":"first","affiliation":[{"name":"Laboratory Department, Dongguan Children\u2019s Hospital","place":["Dongguan, Guangdong, China"]},{"name":"Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics","place":["Dongguan, Guangdong, China"]},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan","place":["Dongguan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Peng","sequence":"additional","affiliation":[{"name":"Laboratory Department, Dongguan Children\u2019s Hospital","place":["Dongguan, Guangdong, China"]},{"name":"Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics","place":["Dongguan, Guangdong, China"]},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan","place":["Dongguan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen","family":"Lv","sequence":"additional","affiliation":[{"name":"Laboratory Department, Dongguan Children\u2019s Hospital","place":["Dongguan, Guangdong, China"]},{"name":"Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics","place":["Dongguan, Guangdong, China"]},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan","place":["Dongguan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Zeng","sequence":"additional","affiliation":[{"name":"Laboratory Department, Dongguan Children\u2019s Hospital","place":["Dongguan, Guangdong, China"]},{"name":"Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics","place":["Dongguan, Guangdong, China"]},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan","place":["Dongguan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory Department, Dongguan Children\u2019s Hospital","place":["Dongguan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siping","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory Department, Dongguan Children\u2019s Hospital","place":["Dongguan, Guangdong, China"]},{"name":"Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics","place":["Dongguan, Guangdong, China"]},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan","place":["Dongguan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Lu","sequence":"additional","affiliation":[{"name":"Laboratory Department, Dongguan Children\u2019s Hospital","place":["Dongguan, Guangdong, China"]},{"name":"Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics","place":["Dongguan, Guangdong, China"]},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan","place":["Dongguan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e64064","DOI":"10.1002\/ajmg.a.64064","article-title":"LARS2\u2010Related perrault syndrome in siblings with 46, XY differences of sex development","author":"Adam","year":"2025","journal-title":"Am. 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