The skeletal ciliopathies are a heterogeneous group of disorders with a significant clinical and genetic variability and the main clinical features are thoracic hypoplasia and short tubular bones. To date, 25 genes have been identified in association with skeletal ciliopathies. Mutations in the KIAA0753 gene have recently been associated with Joubert syndrome (JBTS) and orofaciodigital (OFD) syndrome. We report biallelic pathogenic variants in KIAA0753 in four patients with short-rib type skeletal dysplasia. The manifestations in our patients are variable and ranging from fetal lethal to viable and moderate skeletal dysplasia with narrow thorax and abnormal metaphyses. We demonstrate that KIAA0753 is expressed in normal fetal human growth plate and show that the affected fetus, with a compound heterozygous frameshift and a nonsense mutation in KIAA0753, has an abnormal proliferative zone and a broad hypertrophic zone. The importance of KIAA0753 for normal skeletal development is further confirmed by our findings that zebrafish embryos homozygous for a nonsense mutation in kiaa0753 display altered cartilage patterning.

Oral cancer is challenging for clinicians due to its high mortality and increasing incidence rate. Cyclooxygenase-2 (COX-2) is extensively expressed in oral cancer and oral premalignant lesions and seems to be enhanced specifically in high-risk oral lesions. Mounting evidence suggests that these inhibitors may represent a promising approach for chemoprevention or treatment of oral cancer. This review reports on Medline and PubMed literature searches of published articles from 1995 to 2003. Our purpose is to provide a comprehensive examination and discussion of the potential role of COX-2 in oral cancer development and the use of COX-2 inhibitors for oral cancer chemoprevention or treatment. The data in the literature strongly indicate that COX-2 is significantly upregulated in oral cancer and premalignant lesions, and we believe that inhibition of COX-2 would suppress development of oral lesions by affecting several pathways of oral carcinogenesis. Therefore, the COX-2 inhibitors should be investigated as a new treatment, particularly new chemoprevention agents, for patients who are at high risk for developing oral cancer.

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