RESUMO
BACKGROUND: Skeletal development and maintenance are complex processes known to be coordinated by multiple genetic and epigenetic signaling pathways. However, the role of long non-coding RNAs (lncRNAs), a class of crucial epigenetic regulatory molecules, has been under explored in skeletal biology. RESULTS: Here we report a young patient with short stature, hypothalamic dysfunction and mild macrocephaly, who carries a maternally inherited 690 kb deletion at Chr.1q24.2 encompassing a noncoding RNA gene, DNM3OS, embedded on the opposite strand in an intron of the DYNAMIN 3 (DNM3) gene. We show that lncRNA DNM3OS sustains the proliferation of chondrocytes independent of two co-cistronic microRNAs miR-199a and miR-214. We further show that nerve growth factor (NGF), a known factor of chondrocyte growth, is a key target of DNM3OS-mediated control of chondrocyte proliferation. CONCLUSIONS: This work demonstrates that DNM3OS is essential for preventing premature differentiation of chondrocytes required for bone growth through endochondral ossification.
RESUMO
Patients with trisomies or duplications of distal 15q have rarely been reported in the literature. Previous authors [Zollino et al., 1999: Am J Med Genet 87:391-394] have described a distal 15q trisomy syndrome, including the unusual features of prenatal overgrowth, tall stature, macrocephaly, and craniosynostosis. We report three new patients with a duplication of 15q24-q26.3; features common to the two surviving patients include ptosis, small size, and developmental delay. None of these patients had craniosynostosis or overgrowth. We propose that the previously described distal 15q trisomy syndrome [Zollino et al., 1999: Am J Med Genet 87:391-394] may result from specific disruption of a gene linked to 15q25, rather than partial trisomy for the region.
