1/2. A diagnostic approach to identifying submicroscopic 7p21 deletions in Saethre-Chotzen syndrome: fluorescence in situ hybridization and dosage-sensitive Southern blot analysis.PURPOSE: To report on the use of fluorescence in situ hybridization (FISH) and dosage-sensitive Southern blot analysis in the molecular diagnosis of patients with Saethre-Chotzen syndrome. methods: FISH and dosage-sensitive Southern blot analysis utilizing TWIST gene probes were performed on patients with Saethre-Chotzen syndrome but without an identifiable TWIST sequence variation. RESULTS: Four unrelated patients with a deletion of the TWIST gene were identified by Southern blot; one of them had a complex chromosomal rearrangement involving 7p21 and no apparent deletion by FISH, suggesting a smaller deletion in the region including the TWIST gene. A fifth patient had an abnormal TWIST gene fragment on Southern blot analysis that segregated with the disease in the family; FISH was normal in this patient, suggesting a partial deletion or rearrangement in or near the gene. CONCLUSION: FISH and dosage-sensitive Southern blot analysis are useful diagnostic tools in Saethre-Chotzen syndrome without TWIST sequence variation.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/2. Deletion involving the TWIST locus and the HOXA cluster: a contiguous gene syndrome on 7p?Deletion of TWIST on 7p21 leads to Saethre-Chotzen syndrome, whereas deletion of the HOXA cluster on 7p15.2 leads to hand-foot-genital syndrome. We report here a patient with 46,XY,del(7)(p15.2p21) who had craniosynostosis, maxillary hypoplasia, prominent ear crus, rectoperineal fistula, and hypoplastic fifth fingers. Using fluorescence in situ hybridization, we demonstrated the deletion to encompass the TWIST locus and the HOXA cluster. We suggest that many, if not all, of the features of this patient could be accounted for by combined haploinsufficiency of the TWIST and HOXA cluster. Hence, the patient's phenotype may define a new contiguous gene syndrome on 7p.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |