Rare 19q13.42 duplication encompassing PRKCG associated with neurodevelopmental abnormalities

Duplications at the 19q13.42 region are rare, and the relationship between 19q13.42 duplications and neurodevelopmental phenotypes remains poorly characterized due to the paucity of cases with well-documented clinical features.

Cases with 19q13.42 duplications were reviewed from a cohort of over seventy-five thousand pediatric patients. These patients, suspected of having genetic diseases, underwent next-generation sequencing (NGS) at two collaborating medical centers between 2016 and December 2024. Cases were identified and subjected to further phenotypic and genomic analysis. The reported cases of 19q13.42 duplications were also searched in public resources.

Twenty patients, including 10 cases from our study and 10 cases from public resources with 19q13.42 duplication were enrolled. The duplication breakpoints detected by NGS in internal cases were nonrecurrent and the duplication sizes ranged from 76.864 to 724.194 Kb, which were verified by quantitative real-time polymerase chain reaction (qPCR). Neurodevelopmental disorders (NDDs) were the primary clinical phenotype, present in 94.1% (16/17) of patients. All 16 cases harbored duplications involving PRKCG, of which 12 contained complete gene duplications and 4 involved partial duplications. Genotype-phenotype correlation analysis and the smallest region of overlap (SRO) mapping indicates that PRKCG is a candidate gene underlying the associated NDD phenotypes.

We observed recurrent neurodevelopmental features in a subset of reported 19q13.42 duplications and propose PRKCG as a candidate gene warranting follow-up functional studies. These findings provide a preliminary genotype-phenotype framework for this region, though additional cases with comprehensive clinical phenotyping are required to validate and refine these observations.