Complex balanced intrachromosomal rearrangement involving PITX2 identified as a cause of Axenfeld-Rieger Syndrome

Joseph Farris, Cheryl Khanna, James B. Smadbeck, Sarah H. Johnson, Erick Bothun, Tyler Kaplan, Francis Hoffman, Katarzyna Polonis, Gavin Oliver, Linda M. Reis, Elena V. Semina, Laura Rust, Nicole L. Hoppman, George Vasmatzis, Cherisse A. Marcou, Lisa A. Schimmenti, Eric W. Klee

Research output: Contribution to journalArticlepeer-review

Abstract

Axenfeld-Rieger Syndrome (ARS) type 1 is a rare autosomal dominant condition characterized by anterior chamber anomalies, umbilical defects, dental hypoplasia, and craniofacial anomalies, with Meckel's diverticulum in some individuals. 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 PITX2 or FOXC1. Advanced bioinformatic analysis of the genome data identified a complex, balanced rearrangement disrupting PITX2. 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.

Original languageEnglish
Article numbere63542
JournalAmerican Journal of Medical Genetics, Part A
Volume194
Issue number5
DOIs
StateAccepted/In press - 2024

Keywords

  • Axenfeld-Rieger Syndrome
  • PITX2
  • complex chromosomal rearrangement
  • rare disease

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