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Complex balanced intrachromosomal rearrangement involving PITX2 identified as a cause of Axenfeld-Rieger Syndrome. Am J Med Genet A 2024 May;194(5):e63542

Date

01/18/2024

Pubmed ID

38234180

Pubmed Central ID

PMC11003841

DOI

10.1002/ajmg.a.63542

Scopus ID

2-s2.0-85182427833 (requires institutional sign-in at Scopus site)   2 Citations

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.

Author List

Farris J, Khanna C, Smadbeck JB, Johnson SH, Bothun E, Kaplan T, Hoffman F, Polonis K, Oliver G, Reis LM, Semina EV, Rust L, Hoppman NL, Vasmatzis G, Marcou CA, Schimmenti LA, Klee EW

Author

Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Anterior Eye Segment
Eye Abnormalities
Eye Diseases, Hereditary
Female
Forkhead Transcription Factors
Homeodomain Proteins
Humans