Microduplications

Microduplications are small genomic duplications in which a segment of DNA is present in greater copy number than in a reference genome. They span from about one kilobase to several megabases and may involve a single gene, several genes, or noncoding regions. As copy number variations, microduplications arise during DNA replication or recombination and are often mediated by repetitive sequences such as segmental duplications; mechanisms include non-allelic homologous recombination and microhomology-mediated repair. They can occur in germ cells or somatically and may be present in mosaic form.

Detection and interpretation: Microduplications are detected with array-based methods such as array comparative genomic hybridization and SNP arrays, and increasingly with whole-genome or targeted sequencing. Validation by methods like fluorescence in situ hybridization or quantitative PCR is common. Many microduplications are benign polymorphisms; pathogenicity depends on the genes involved, dosage sensitivity, and regulatory elements that may be affected. Clinically relevant duplications typically alter the dosage of dosage-sensitive genes or disrupt regulatory landscapes.

Clinical significance and counseling: Pathogenic microduplications have been associated with neurodevelopmental disorders, congenital anomalies, and variable traits including intellectual disability and autism spectrum features. The impact depends on inheritance, with de novo duplications more often linked to disease, though inherited duplications can be pathogenic or benign. Recurrence risk is influenced by parental testing and the possibility of mosaicism. Several recurrent microduplication regions have been described, including 1q21.1 and 16p11.2, each associated with a spectrum of features.

See also: Copy number variation, dosage sensitivity, microdeletion, genomics.