Academic Journal
High-Resolution Genomic Characterization of WAGR Spectrum Disorder: Insights From a Novel Cohort and Literature Synthesis, and Validation of Patient-Reported Data.
| Τίτλος: | High-Resolution Genomic Characterization of WAGR Spectrum Disorder: Insights From a Novel Cohort and Literature Synthesis, and Validation of Patient-Reported Data. |
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| Συγγραφείς: | George AM; Division of Genetic and Genomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Duki BT; Division of Genetic and Genomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Katz ZS; Division of Genetic and Genomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Viswanathan A; Division of Genetic and Genomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., MacFarland SP; Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; Department of Pediatrics, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.; Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Hathaway ER; Division of Genetic and Genomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Monahan C; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA., Morris J; International WAGR Syndrome Association, Montgomery Village, Maryland, USA., Trout KL; International WAGR Syndrome Association, Montgomery Village, Maryland, USA., Krantz SM; International WAGR Syndrome Association, Montgomery Village, Maryland, USA., Ganguly A; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA., Kalish JM; Division of Genetic and Genomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; Department of Pediatrics, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.; Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. |
| Πηγή: | American journal of medical genetics. Part A [Am J Med Genet A] 2026 Sep; Vol. 200 (9), pp. 1989-1999. Date of Electronic Publication: 2026 Apr 12. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | 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- |
| Ιατρικοί όροι (MeSH): | WAGR Syndrome*/genetics , WAGR Syndrome*/diagnosis , WAGR Syndrome*/pathology, Chromosomes, Human, Pair 11/genetics ; Polymorphism, Single Nucleotide/genetics ; Wilms Tumor/genetics ; Humans ; Female ; Comparative Genomic Hybridization ; Male ; Chromosome Deletion ; Cohort Studies ; Child, Preschool ; Phenotype ; Genetic Association Studies ; Infant ; Child ; Genomics |
| Περίληψη: | WAGR spectrum disorder (WAGRSD) is an ultra-rare congenital disorder caused by heterozygous deletion of chromosome 11p13. While classically associated with Wilms tumor, Aniridia, Genitourinary anomalies, and a Range of developmental delays, accurate delineation of the deletion is critical for prognosis because the phenotypic spectrum extends well beyond this tetrad. To improve diagnostic resolution, we developed and validated a high-density custom CGH-SNP array for precise breakpoint mapping of 11p13. We present a molecularly confirmed cohort of 23 new patients and integrate these with 91 published cases, forming the largest combined cohort to date (N = 114) with detailed genotype-phenotype information. Key findings include: (1) the custom array provided superior genomic resolution compared to standard clinical arrays; (2) seven patients (6.1%) were found to have a dual diagnosis of WAGRSD and Potocki-Shaffer syndrome (PSS)-a contiguous-gene syndrome characterized by multiple osteochondromas that requires distinct surveillance; (3) in 42 patients with fully defined deletions (n = 42, 38% of the cohort), no statistically significant association was observed between deletion of LMO2 (or other candidate genes) and Wilms tumor risk; and (4) phenotypic frequencies in this medically validated cohort closely aligned with prior caregiver-reported registry data, validating patient-driven registries as a reliable resource for rare disease research. Together, these findings underscore the necessity of high-resolution genomic testing to guide counseling, refine anticipatory management-including screening for PSS-related complications-and expand the phenotypic understanding of 11p13 deletion disorders. (© 2026 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.) |
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| Grant Information: | International WAGR Syndrome Association; Miranda's Mission; WAGR Warriors; Miranda Morris WAGR Spectrum Research Fund at the Children's Hospital of Philadelphia |
| Contributed Indexing: | Keywords: 11p13 deletion; WAGR spectrum disorder (WAGRSD); WAGR syndrome; Wilms tumor; high resolution genomic array |
| Entry Date(s): | Date Created: 20260413 Date Completed: 20260804 Latest Revision: 20260804 |
| Update Code: | 20260804 |
| DOI: | 10.1002/ajmg.a.70159 |
| PMID: | 41968606 |
| Βάση Δεδομένων: | MEDLINE |
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