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Title: Locus heterogeneity for Waardenburg syndrome is predictive of clinical subtypes

Waardenburg syndrome (WS) is a dominantly inherited and clinically variable syndrome of deafness, pigmentary changes, and distinctive facial features. Clinically, WS type I (WS1) is differentiated from WS type II (WS2) by the high frequency of dystopia canthorum in the family. In some families, WS is caused by mutations in the PAX3 gene on chromosome 2q. We have typed microsatellite markers within and flanking PAX3 in 41 WS1 kindreds and 26 WS2 kindreds in order to estimate the proportion of families with probable mutations in PAX3 and to study the relationship between phenotypic and genotypic heterogeneity. Evaluation of heterogeneity in location scores obtained by multilocus analysis indicated that WS is linked to PAX3 in 60% of all WS families and in 100% of WS1 families. None of the WS2 families were linked. In those families in which equivocal lod scores (between -2 and +1) were found, PAX3 mutations have been identified in 5 of the 15 WS1 families but in none of the 4 WS2 families. Although preliminary studies do not suggest any association between the phenotype and the molecular pathology in 20 families with known PAX3 mutations and in four patients with chromosomal abnormalities in the vicinity of PAX3,more » the presence of dystopia in multiple family members is a reliable indicator for identifying families likely to have a defect in PAX3. 59 refs., 3 figs., 5 tabs.« less
Authors:
;  [1] ;  [2] ; ;  [3] ; ;  [4] ;  [5] ;  [6]
  1. Boston Univ. School of Medicine, MA (United States)
  2. Galludet Univ., Washington, DC (United States)
  3. Michigan State Univ., East Lansing, MI (United States)
  4. National Institute on Deafness and Other Communication Disorders, Bethesda, MD (United States)
  5. Univ. of Cape Town (South Africa)
  6. and others
Publication Date:
OSTI Identifier:
35504
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Journal of Human Genetics; Journal Volume: 55; Journal Issue: 4; Other Information: PBD: Oct 1994
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; HUMAN CHROMOSOME 2; GENETIC MAPPING; CHROMOSOMAL ABERRATIONS; HUMAN POPULATIONS; SENSE ORGANS DISEASES; HEREDITARY DISEASES; GENE MUTATIONS; PHENOTYPE; GENOTYPE; STATISTICAL MODELS