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. 1992 May;50(5):902–913.

Waardenberg syndrome (WS) type I is caused by defects at multiple loci, one of which is near ALPP on chromosome 2: First report of the WS consortium

Lindsay A Farrer, Kenneth M Grundfast, Jean Amos, Kathleen S Arnos, James H Asher, Peter Beighton, Scott R Diehl, Jörgen Fex, Carole Foy, Thomas B Friedman, Jacquie Greenberg, Christopher Hoth, Mary Marazita, Aubrey Milunsky, Robert Morell, Walter Nance, Valerie Newton, Rajkumar Ramesar, Theresa B San Agustin, James Skare, Cathy A Stevens, Ronald G Wagner, Edward R Wilcox, Ingrid Winship, Andrew P Read
PMCID: PMC1682585  PMID: 1349198

Abstract

Previous studies have localized the gene for Waardenburg syndrome (WS) type I to the distal portion of chromosome 2q, near the ALPP locus. We pooled linkage data obtained from 41 WS type I and 3 WS type II families which were typed for six polymorphic loci on chromosome 2q in order to refine the location of the WS locus (WS1) and evaluate the extent of genetic heterogeneity. In the course of this work, we developed diagnostic criteria for genetic and phenotypic studies. Our findings, based on two-locus and multilocus analysis using a linkage map established from reference pedigrees, suggest that there are two or more mutations causing WS, one of which (i.e., WS1) is located on chromosome 2q, between the ALPP and FN1 loci, at distances of 7.8 cM and 11.2 cM for each marker, respectively. The results also indicate that WS1 is responsible for the illness in approximately 45% of all families in this sample. However, the odds favoring this position over a location between ALPP and SAG are only 2:1 when alternate assumptions about the proportion of linked families are considered. We conclude that a more saturated map of this region of chromosome 2q, including highly polymorphic markers, will be needed to accurately distinguish linked families and, ultimately, isolate the mutant gene.

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Selected References

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