Waardenburg's syndrome (WS) is an autosomal dominant hereditary disorder with variable penetrance and expressivity. The full syndrome is characterized by dystopia canthorum, heterochromia iridis, pigment disorders of hair and skin, and congenital deafness. Waardenburg's syndrome is of three types, one with and one without dystopia canthorum and the third, pseudo-Waardenburg's syndrome. Various combinations of two or more signs can occur. Additional symptoms can be present in some cases. Waardenburg's syndrome with deafness occurs with a frequency of two cases per 100,000 general population and represents 2-5% of cases of profound childhood deafness. The long term objective of this study is to understand the basic mechanism underlying Waardenburg's syndrome which causes profound deafness. Specifically, the goal of this proposal is to confirm the location of the gene responsible for Waardenburg's syndrome on human chromosome 2q and to identify tightly linked flanking DNA markers. Nine families with WS type I and two cases of WS type II with mental retardation have been clinically verified. Lymphoblast cell lines from these family members are established for long term genetic study. Screening these WS families with PFLP DNA markers are currently under way in our laboratory. Also, we will examine the WS type II to answer the question whether WS type I and type II are caused by the same entity and arise from the different defects of the gene. The experimental methods include the establishment of lymphoblastoid cell lines, isolation of high molecular weight DNA, Southern blot as well as traditional linkage analysis with restriction fragment length polymorphism.
