Tissue specific trisomy 15 mosaicism associated with urogenital malformations

Agneta Nordenskjöld; Kristina Lagerstedt-Robinson; Britt-Marie Anderlid; Johanna Lundin

doi:10.1016/j.ejmg.2023.104824

Tissue specific trisomy 15 mosaicism associated with urogenital malformations

Eur J Med Genet. 2023 Oct;66(10):104824. doi: 10.1016/j.ejmg.2023.104824. Epub 2023 Aug 25.

Authors

Agneta Nordenskjöld¹, Kristina Lagerstedt-Robinson², Britt-Marie Anderlid³, Johanna Lundin⁴

Affiliations

¹ Department of Women's and Children's Health and Center for Molecular Medicine, Karolinska Institutet, SE-17176, Stockholm, Sweden; Paediatric Surgery, Astrid Lindgren Children Hospital, Karolinska University Hospital, SE-17176, Stockholm, Sweden. Electronic address: agneta.nordenskjold@ki.se.
² Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, SE-17176, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, SE-17176, Stockholm, Sweden. Electronic address: kristina.lagerstedt@ki.se.
³ Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, SE-17176, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, SE-17176, Stockholm, Sweden. Electronic address: britt.marie.anderlid@ki.se.
⁴ Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, SE-17176, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, SE-17176, Stockholm, Sweden. Electronic address: johanna.lundin@ki.se.

PMID: 37633646
DOI: 10.1016/j.ejmg.2023.104824

Abstract

We describe a boy born with hypospadias and later diagnosed with vesicoureteral reflux and mild cognitive disability. Routine diagnostic investigation by karyotyping, chromosomal microarray (CMA) and trio analysis with whole exome sequencing was normal. However, later CMA performed on DNA from genital tissue showed trisomy 15, which prompted further analysis. Fluorescent in situ hybridization was performed to verify the CMA result and delineate the mosaic rate. Methylation specific MLPA was performed to investigate the parent of origin of the extra chromosome 15. Further medical examination of the boy identified fine Blaschko's lines, indicative of mosaicism, but earlier unnoticed. CMA on genital tissue showed 80% mosaicism for trisomy 15. Bladder mucosa and muscle showed a high degree of trisomy 15 (56% and 45% respectively), while buccal mucosa and abdominal skin showed low-grade or no trisomy 15. The extra chromosome 15 was of maternal origin. This case report describes a boy with two different malformations in the same organ region that carries a high degree of trisomy 15 mosaicism. Hence, the clinical implication is that there is no recurrence risk for sibs, but the boy in his turn risks producing gametes with an extra chromosome 15. Tissue restricted mutations are not commonly described but may cause congenital malformations that affects the information to the family.

Keywords: Congenital malformations; Hypospadias; Mosaicism; Trisomy 15; Vesicoureteral reflux.