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Keywords: Genotype-phenotype correlations; Chromosomal abnormalities; Copy number/structural variation; Dysmorphology

F.T. Bellucco; B. Favilla; E. Perrone; M.I. Melaragno

Affiliation: Department of Morphology and Genetics, UNIFESP - Universidade Federal de São Paulo, São Paulo, Brazil

Several patients with 5p duplication and 15q deletion have been reported in the literature, involving different chromosome regions and great variations in their clinical features. To the best of our knowledge, partial trisomy 5p associated with monosomy 15q was never reported. Here, we describe a family, characterized by G-banding karyotype and array technique, in which we identified a 30 Mb 5p15.33p13.3 duplication and a 2.5 Mb 15q26.3 deletion in three individuals (two siblings and their paternal uncle), due to a balanced familial translocation between 5p and 15q (found in the father and in the paternal grandmother). The siblings present neurodevelopment delay, intellectual disability, short stature, facial dysmorphisms (such as downslanting palpebral fissures, retrognathia and downturned corners of mouth), short neck, and brachydactyly with 5th finger clinodactyly. Although the boy presents obesity and hyperphagia, like his uncle, the girl does not present these phenotypes. Instead, she presents convergent strabismus and ocular hypertelorism, which were not identified in her brother. Duplications at 5p13.3-5p15.33 region result in mild and relatively indistinct phenotypes, in comparison with duplication at 5p10-5p13.1 segment including the NIPBL gene, which results in a more severe phenotype. Chromosome rearrangements involving 15q26, on the other hand, are often related to multiple congenital anomalies, such as growth delay, learning disabilities, unusual facial features and anomalies of the hands and feet. One of the most important genes that seems to be responsible for 15q26 deletion phenotype is the IGF1R gene, which has already been associated with growth retardation, developmental delay, clinodactyly, and brachydactyly. Despite presenting such phenotypes, our patients’ deletion does not include IGF1R gene. They show a combination of phenotypic findings of both 5p duplication and 15q deletions described in the literature thus far. However, the genotype-phenotype correlation is still challenging, since there is no phenotype concordance among the patients, even between both siblings, who have the exact same rearrangement. These data emphasize the importance of detailed cytogenomic and clinical analyses for an accurate diagnosis, prognosis, and genetic counseling and provide an opportunity to improve genotype-phenotype correlations of partial 5p duplication and 15q deletion syndrome patients. Financial Support: FAPESP, Brazil.