How to cite this article: Tüysüz B, Collin A, Arapoğlu M, Suyugül N. 2009. Clinical variability of Waardenburg–Shah syndrome in patients with proximal 13q deletion syndrome including the endothelin-B receptor locus. Am J Med Genet Part A 149A:2290–2295.
Clinical variability of Waardenburg–Shah syndrome in patients with proximal 13q deletion syndrome including the endothelin-B receptor locus†
Article first published online: 16 SEP 2009
Copyright © 2009 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 149A, Issue 10, pages 2290–2295, October 2009
How to Cite
Tüysüz, B., Collin, A., Arapoğlu, M. and Suyugül, N. (2009), Clinical variability of Waardenburg–Shah syndrome in patients with proximal 13q deletion syndrome including the endothelin-B receptor locus. Am. J. Med. Genet., 149A: 2290–2295. doi: 10.1002/ajmg.a.33031
- Issue published online: 24 SEP 2009
- Article first published online: 16 SEP 2009
- Manuscript Accepted: 21 JUN 2009
- Manuscript Received: 19 MAY 2008
- 13q deletion;
- Hirschsprung disease;
- Waardenburg–Shah syndrome;
- clinical variability
Waardenburg–Shah syndrome (Waardenburg syndrome type IV-WS4) is an auditory-pigmentary disorder that combines clinical features of pigmentary abnormalities of the skin, hair and irides, sensorineural hearing loss, and Hirschsprung disease (HSCR). Mutations in the endothelin-B receptor (EDNRB) gene on 13q22 have been found to cause this syndrome. Mutations in both alleles cause the full phenotype, while heterozygous mutations cause isolated HSCR or HSCR with minor pigmentary anomalies and/or sensorineural deafness. We investigated the status of the EDNRB gene, by FISH analysis, in three patients with de novo proximal 13q deletions detected at cytogenetic analysis and examined the clinical variability of WS4 among these patients. Chromosome 13q was screened with locus specific FISH probes and breakpoints were determined at 13q22.1q31.3 in Patients 1 and 3, and at 13q21.1q31.3 in Patient 2. An EDNRB specific FISH probe was deleted in all three patients. All patients had common facial features seen in proximal 13q deletion syndrome and mild mental retardation. However, findings related to WS4 were variable; Patient 1 had hypopigmentation of the irides and HSCR, Patient 2 had prominent bicolored irides and mild bilateral hearing loss, and Patient 3 had only mild unilateral hearing loss. These data contribute new insights into the pathogenesis of WS4. © 2009 Wiley-Liss, Inc.