Complex balanced intrachromosomal rearrangement involving PITX2 identified as a cause of Axenfeld-Rieger Syndrome.
| Title: | Complex balanced intrachromosomal rearrangement involving PITX2 identified as a cause of Axenfeld-Rieger Syndrome. |
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| Authors: | Farris J; Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.; Khanna C; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA.; Smadbeck JB; Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.; Johnson SH; Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.; Bothun E; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA.; Kaplan T; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA.; Hoffman F; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.; Polonis K; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.; Oliver G; Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.; Reis LM; Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin and Children's Wisconsin, Milwaukee, Wisconsin, USA.; Semina EV; Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin and Children's Wisconsin, Milwaukee, Wisconsin, USA.; Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.; Rust L; Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA.; Hoppman NL; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.; Vasmatzis G; Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA.; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.; Marcou CA; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.; Schimmenti LA; Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA.; Klee EW; Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA. |
| Source: | American journal of medical genetics. Part A [Am J Med Genet A] 2024 May; Vol. 194 (5), pp. e63542. Date of Electronic Publication: 2024 Jan 17. |
| Publication Type: | Case Reports; Journal Article |
| Language: | English |
| Journal Info: | Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 101235741 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-4833 (Electronic) Linking ISSN: 15524825 NLM ISO Abbreviation: Am J Med Genet A Subsets: MEDLINE |
| Imprint Name(s): | Publication: Hoboken, N.J. : Wiley-Blackwell; Original Publication: Hoboken, N.J. : Wiley-Liss, c2003- |
| MeSH Terms: | Anterior Eye Segment*/abnormalities ; Eye Abnormalities*/diagnosis ; Eye Abnormalities*/genetics ; Eye Abnormalities*/pathology ; Eye Diseases, Hereditary*/diagnosis ; Eye Diseases, Hereditary*/genetics ; Eye Diseases, Hereditary*/pathology ; Homeobox Protein PITX2*; Forkhead Transcription Factors/genetics ; Homeodomain Proteins/genetics ; Female ; Humans |
| 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.; (© 2024 Wiley Periodicals LLC.) |
| References: | J Med Genet. 2023 Apr;60(4):368-379. (PMID: 35882526); Trans Am Ophthalmol Soc. 1983;81:736-84. (PMID: 6676983); Cancer Genet. 2018 Feb;221:1-18. (PMID: 29405991); Nat Genet. 1996 Dec;14(4):392-9. (PMID: 8944018); Dev Dyn. 2000 May;218(1):195-200. (PMID: 10822271); Clin Genet. 2018 Jun;93(6):1123-1130. (PMID: 28972279); Hum Mol Genet. 2005 Nov 15;14(22):3347-59. (PMID: 16203745); Front Genet. 2023 Jan 10;13:1085139. (PMID: 36712854); Am J Hum Genet. 1996 Dec;59(6):1297-305. (PMID: 8940275); Surv Ophthalmol. 1985 May-Jun;29(6):387-409. (PMID: 3892740); Birth Defects Res A Clin Mol Teratol. 2004 Feb;70(2):82-91. (PMID: 14991915); Bioinformatics. 2014 Jun 1;30(11):1627-9. (PMID: 24526710); Mol Syndromol. 2015 Sep;6(3):110-34. (PMID: 26732513); Eur J Hum Genet. 2012 Dec;20(12):1224-33. (PMID: 22569110); Front Genet. 2020 Jul 20;11:688. (PMID: 32765580); Hum Mol Genet. 2017 Sep 15;26(18):3630-3638. (PMID: 28911203); Cell Stem Cell. 2019 May 2;24(5):736-752.e12. (PMID: 30982769); Nature. 2022 Apr;604(7905):310-315. (PMID: 35388217); PLoS One. 2016 Apr 28;11(4):e0153757. (PMID: 27124303); Genomics. 1998 Feb 1;47(3):409-13. (PMID: 9480756); Invest Ophthalmol Vis Sci. 2011 Mar 18;52(3):1450-9. (PMID: 20881290); Am J Hum Genet. 2017 Aug 3;101(2):206-217. (PMID: 28735859) |
| Grant Information: | R01 EY015518 United States EY NEI NIH HHS; United States NH NIH HHS |
| Contributed Indexing: | Keywords: Axenfeld‐Rieger Syndrome; PITX2; complex chromosomal rearrangement; rare disease |
| Substance Nomenclature: | 0 (Forkhead Transcription Factors); 184787-43-7 (Homeobox Protein PITX2); 0 (Homeodomain Proteins); 0 (PITX2 protein, human) |
| SCR Disease Name: | Axenfeld-Rieger syndrome |
| Entry Date(s): | Date Created: 20240118 Date Completed: 20240411 Latest Revision: 20250502 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11003841 |
| DOI: | 10.1002/ajmg.a.63542 |
| PMID: | 38234180 |
| Database: | MEDLINE |
Case Reports; Journal Article