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Here, we describe a clinically ascertained female of childbearing age with ARS for whom clinical targeted sequencing and deletion\/duplication analysis followed by clinical exome and genome sequencing resulted in no pathogenic variants or variants of unknown significance in <jats:italic>PITX2<\/jats:italic> or <jats:italic>FOXC1<\/jats:italic>. Advanced bioinformatic analysis of the genome data identified a complex, balanced rearrangement disrupting <jats:italic>PITX2<\/jats:italic>. This case is the first reported intrachromosomal rearrangement leading to ARS, illustrating that for patients with compelling clinical phenotypes but negative genomic testing, additional bioinformatic analysis are essential to identify subtle genomic abnormalities in target genes.<\/jats:p>","DOI":"10.1002\/ajmg.a.63542","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T07:38:40Z","timestamp":1705563520000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Complex balanced intrachromosomal rearrangement involving <scp><i>PITX2<\/i><\/scp> identified as a cause of <scp>Axenfeld\u2010Rieger<\/scp> Syndrome"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7691-8334","authenticated-orcid":false,"given":"Joseph","family":"Farris","sequence":"first","affiliation":[{"name":"Center for Individualized Medicine Mayo Clinic  Rochester Minnesota 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