Genetic and Clinical Profiles of Spondylocostal Dysostosls Patients in Taiwan

摘要

Spondylocostal dysostosis (SCD [OMIM 277300]) comprises a heterogeneous group of disorders characterized by multiple vertebral anomalies, including hemi-vertebrae and segments of vertebrae accompanied by anomalies of the ribs [Bulman et al., 2000]. Patients generally have no family history of the condition and show diverse clinical and radiological findings. However, the basis of these defects in some cases stems from disturbances in the Notch signaling pathway that plays a central role in somite formation [Weinmaster, 2000]. The Notch signaling pathway is an evolutio-narily conserved signal-transduction pathway that has important roles throughout embryonic development, as well as in the origins of diseases like cancer [Harper et al., 2003].In humans, the first autosomal recessive genetic mutation closely related to SCD was identified in the DLL3 gene [Bulman et al., 2000]. Subsequently, three other Notch signaling pathway genes (MESP2, LFNG and HES7) have been associated with SCD [Whittock et al., 2004; Sparrow et al., 2006, 2008]. Mutations in DLL3, include nonsense, missense, frameshift, and splice-site mutations, specify functionally deficient products [Sparrow et al., 1998; Bulman et al., 2000; Bonafe et al., 2003; Turnpenny and Kusumi, 2003].