Citogenomic investigation in patients with developmental delay and pigmentary mosaicism

Author(s)

Yanca Gasparini de Oliveira

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2023-03-17

Examining board members

Leslie Domenici Kulikowski; Maria Esther Jurfest Rivero Ceccon; Monica Vannucci Nunes Lipay; Emi Zuiki Murano

• Advisor: Leslie Domenici Kulikowski

Abstract

Mosaicism is a frequent event in the general population, whose frequency in cases that lead to phenotypic effects is estimated at approximately 1 in 10.000 live births. However, it is poorly identified due to the difficulty of cytogenetic and molecular characterization that can occur in different cell populations. The detection of genomic alterations in different tissues using cytogenomic techniques can reveal important elements for understanding the relationship between genomic architecture and its phenotypic effect, thus helping in the diagnostic conclusion of patients with global developmental delay and pigmentary mosaicism. We studied 21 sets of samples from patients with GDD/PM (14 females and 7 males) by G-banding and genomic array, totaling 84 samples. Our study revealed 39 alterations classified as pathogenic or probably pathogenic, allowing the diagnosis of 13/21 patients in this study. We observed that the skin (fibroblasts) was the tissue with the highest number of pathogenic alterations, a fact related to pigmentary mosaicism, and we emphasize that the genomic array was essential for the unequivocal molecular characterization of each cell population, given the ease of obtaining of DNA from any type of sample. It was also possible to observe that the genomic array enabled the diagnosis of patients and the detection of mosaicism at different levels. In conclusion, our study showed that the genotype-phenotype association, considering different tissues, is essential for the diagnostic routine of patients with GDD/PM. As well as improving the understanding of the role of gene dosage, inter and intra-tissue, and its relationship with clinical manifestations (AU)

• FAPESP's process: 18/20936-4 - Cytogenomic investigation in patients with global development delay and pigmentary mosaicism
• Grantee: Yanca Gasparini de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)