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| LOCUS HETEROGENEITY FOR WAARDENBURG SYNDROME IS PREDICTIVE OF CLINICAL SUBTYPES |
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| Author(s): FARRER LA, ARNOS KS, ASHER JH, BALDWIN CT, DIEHL SR, FRIEDMAN TB, GREENBERG J, GRUNDFAST KM, HOTH C, LALWANI AK, LANDA B, LEVERTON K, MILUNSKY A, MORELL R, NANCE WE, NEWTON V, RAMESAR R, RAO VS, REYNOLDS JE, SANAGUSTIN TB, WILCOX ER, WINSHIP I, READ AP |
| Source: AMERICAN JOURNAL OF HUMAN GENETICS Volume: 55 Issue: 4 Pages: 728-737 Published: OCT 1994 |
| Times Cited: 44 References: 59 |
| Abstract: 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, the presence of dystopia in multiple family members is a reliable indicator for identifying families likely to have a defect in PAX3. |
| Document Type: Article |
| Language: English |
| Reprint Address: FARRER, LA (reprint author), BOSTON UNIV, SCH MED, DEPT NEUROL, 80 E CONCORD ST, BOSTON, MA 02118 USA |
Addresses:
1. BOSTON UNIV, SCH MED, DEPT BIOSTAT & EPIDEMIOL, BOSTON, MA 02118 USA
2. BOSTON UNIV, SCH MED, CTR HUMAN GENET, BOSTON, MA 02118 USA
3. GALLAUDET UNIV, WASHINGTON, DC 20002 USA
4. MICHIGAN STATE UNIV, DEPT ZOOL, E LANSING, MI 48824 USA
5. MICHIGAN STATE UNIV, GRAD PROGRAM GENET, E LANSING, MI 48824 USA
6. NIDR, EPIDEMIOL & ORAL DIS PREVENT PROGRAM, MOLEC EPIDEMIOL & DIS INDICATORS BRANCH, BETHESDA, MD 20892 USA
7. NIDOCD, MOLEC OTOL LAB, BETHESDA, MD USA
8. UNIV CAPE TOWN, DEPT HUMAN GENET, CAPE TOWN 7925, SOUTH AFRICA
9. VIRGINIA COMMONWEALTH UNIV, DEPT HUMAN GENET, RICHMOND, VA USA
10. UNIV MANCHESTER, DEPT MED GENET, MANCHESTER, LANCS ENGLAND
11. UNIV MANCHESTER, CTR AUDIOL, MANCHESTER, LANCS ENGLAND |
| Publisher: UNIV CHICAGO PRESS, 5720 S WOODLAWN AVE, CHICAGO, IL 60637 |
| Subject Category: Genetics & Heredity |
| IDS Number: PJ027 |
| ISSN: 0002-9297 |
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