A conference, sponsored by the National Institute on Deafness and other Communicative Disorders, was held in New York on 27 September 1990, with the aim of establishing greater communication between research groups working on this syndrome or its mouse homologue. As a result the participants agreed to form a consortium to pursue two aspects of the work:
a) to establish a consensus opinion on the clinical criteria used to diagnose the different types of Waardenburg syndrome;
b) to search for linkage in the region of the gene for WS-1 at chromosomal position 2q37, applying an agreed six probes to the families available to each research group.
At a follow up meeting in Bethesda in April 1991 progress was reviewed. Forty Waardenburg syndrome families had been typed for some or all of the six polymorphisms. The combined data show that the syndrome is genetically heterogeneous. Families could be divided into three groups:
a) those showing tight linkage to probe ALPP;
b) those giving strong negative lod scores with respect to ALPP; and
c) those with one or two recombinants between the syndrome and ALPP but where the family is not big enough to define the linkage within the family.
ALPP remains the best marker for Waardenburg syndrome on chromosome 2. It seem likely that the chromosome 2 locus in man is the homologue of the splotch locus in the mouse, but the map is not yet sufficiently developed in this region for definite proof. ALPP was localised to 2q37 by radioactive in situ hybridisation, but there are now doubts about this and the true location may be more proximal, around 2q35. Further Waardenburg syndrome families are needed, that are well documented clinically and are large enough to study linkage within the single family – ie 15 or more informative meioses. Those who know of such families are asked to contact one of the consortium members – the name and address of the nearest centre can be obtained from Dr J Fex, National Institute on Deafness and other Communications Disorders, National Institutes of Health, Bethesda, USA.