In situ hybridization applied to Waardenburg syndrome

Multilocus linkage analysis has suggested that the Waardenburg syndrome type 1 (WS1) locus is flanked by placental alkaline phosphatase (ALPP) and fibronectin 1 (FN1). We used fluorescence in situ hybridization (FISH) to map ALPI (intestinal alkaline phosphatase) to 2q36.3-q37.1 and FN1 to 2q34. FISH also showed that a WS1 patient with a de novo interstitial deletion of 2q35-q36.1 retained both API and FN1 on the deleted chromosome. The human PAX3 gene has been shown previously to be mutated in at least two WS1 patients. We mapped a PCR product from the PAX3 gene to 2q35 and found it was absent in the deleted chromosome. Thus, our FISH mapping results confirm the conclusions from previous linkage analysis and support the conclusion that mutation of the PAX3 gene can cause Waardenburg syndrome.