Exploring the pathogenicity and genotype-phenotype correlation of 16p13.11 microduplication: a report of two cases

16p13.11 microduplication syndrome is a rare genomic disorder caused by an extra copy of a small segment of DNA on the short arm of chromosome 16 at a specific location in band 13.11. The clinical presentation is highly variable. Some individuals are entirely asymptomatic, while others present with a spectrum of neurodevelopmental disorders.

We report two cases with 16p13.11 microduplication to investigate the genotype-phenotype correlations. Peripheral blood was collected from the two patients and their respective parents and all participants underwent whole exome sequencing. Bioinformatics analysis and pathogenicity assessment were performed for variants as well as next-generation sequencing coverage depth analysis to identify abnormal copy number regions. As a result, a 0.893 Mb duplication of 16p13.11 region (chr16:15380928-16274075) was identified in patient 1, while his father carried a 0.841 Mb duplication in the same region (chr16: 15380928-16221831). In Patient 2, a 1.39 Mb duplication of 16p13.11 region (chr16: 14927699-16317333)-inherited from his father-was identified, as well as a pathogenic heterozygous variant in PRRT2 (exon2: c.649dup, p.R217Pfs*8), which was inherited from his mother.

Our findings underscore the highly incomplete penetrance and phenotypic variability of 16p13.11 microduplication. Future research should focus on the pathogenic mechanisms, explore potential interactions with genes like PRRT2, and establish standardized long-term monitoring strategies for carriers-especially those with comorbid pathogenic variants-to enhance clinical management and genetic counseling.