A rare case of a boy with de novo microduplication at 5q35.2q35.3 from central Brazil

Genomic disorders are genetic diseases that are caused by rearrangements of chromosomal material via deletions, duplications, and inversions of unique genomic segments at specific regions. Such rearrangements could result from recurrent non-allelic homologous recombination between low copy repeats. In cases where the breakpoints flank the low copy repeats, deletion of chromosomal segments is often followed by reciprocal duplication. Variations in genomic copy number manifest differently, with duplication and deletions of the same genomic region showing opposite phenotypes. Sotos syndrome is caused by alterations in the dosage of NSD1 on human chromosome 5 by either deletions or mutations, such as microdeletion of 5q35.2q35.3. In general, patients carrying reciprocal microduplication at 5q35.2q35.3 present no clinical phenotype or milder phenotype than do patients with microdeletion at the same locus. We report the first case of 5q35.2q35.3 microduplication encompassing NSD1 in a patient from central Brazil. We identified a genomic imbalance corresponding to a de novo 0.45 Mb microduplication at 5q35.2q35.3 by chromosomal microarray analysis and study of low-copy repeats. The proband had microduplication in the chromosomal region containing NSD1, which resulted in a Sotos syndrome reversed phenotype, and this duplication was associated with microcephaly, short stature, and developmental delay. Analysis of the genomic structure of the rearranged 5q35.2q35.3 chromosomal region revealed two major low-copy repeat families, which caused the recurrent rearrangements. Chromosomal microarray analysis is a potential tool to identify microrearrangements and guide medical diagnosis, which has to be followed by a non-directive genetic counseling approach to improve the quality of life of the patient.