Short stature, digit anomalies and dysmorphic facial features are associated with the duplication of miR-17 ~ 92 cluster.

MicroRNAs (miRNAs) are key regulators of gene expression, playing important roles in development, homeostasis, and disease. Recent experimental evidence indicates that mutation or deregulation of the MIR17HG gene (miR-17 ~ 92 cluster) contributes to the pathogenesis of a variety of human diseases, including cancer and congenital developmental defects. We report on a 9-year-old boy who presented with developmental delay, autism spectrum disorder, short stature, mild macrocephaly, lower facial weakness, hypertelorism, downward slanting palpebral fissures, brachydactyly, and clinodactyly. SNP-microarray analysis revealed 516 kb microduplication at 13q31.3 involving the entire MIR17HG gene encoding the miR-17 ~ 92 polycistronic miRNA cluster, and the first five exons of the GPC5 gene. Family study confirmed that the microduplication was maternally inherited by the proband and one of his five half-brothers; digit and other skeletal anomalies were exclusive to the family members harboring the microduplication. This case represents the smallest reported microduplication to date at 13q31.3 and provides evidence supporting the important role of miR-17 ~ 92 gene dosage in normal growth and skeletal development. We postulate that any dosage abnormality of MIR17HG, either deletion or duplication, is sufficient to interrupt skeletal developmental pathway, with variable outcome from growth retardation to overgrowth.