Homozygous and heterozygous inheritance of PAX3 mutations causes different types of Waardenburg syndrome
Article first published online: 15 MAY 2003
Copyright © 2003 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 122A, Issue 1, pages 42–45, 15 September 2003
How to Cite
Wollnik, B., Tukel, T., Uyguner, O., Ghanbari, A., Kayserili, H., Emiroglu, M. and Yuksel-Apak, M. (2003), Homozygous and heterozygous inheritance of PAX3 mutations causes different types of Waardenburg syndrome. Am. J. Med. Genet., 122A: 42–45. doi: 10.1002/ajmg.a.20260
- Issue published online: 25 AUG 2003
- Article first published online: 15 MAY 2003
- Manuscript Accepted: 27 FEB 2003
- Manuscript Received: 20 SEP 2002
- Waardenburg syndrome;
- Klein–Waardenburg syndrome;
- PAX3 mutations;
- clinical variability
Type I Waardenburg syndrome (WS-I) is an auditory-pigmentary syndrome caused by heterozygous loss of function mutations in the PAX3 gene. Klein–Waardenburg syndrome (WS-III) is a very rare condition and represents an extreme presentation of WS-I, additionally associated with musculoskeletal abnormalities. We present an 18-months old Turkish child with typical Klein–Waardenburg syndrome (WS) including dystopia canthorum, partial albinism, and upper-limb defects. The child was born to a consanguineous couple and both parents had WS-I. We screened the entire coding region of the PAX3 gene for mutations and identified a novel missense mutation, Y90H, within the paired box domain of PAX3. Both parents were heterozygous for the mutation and the proposita was homozygous. This is the third report of a homozygous PAX3 mutation causing the WS-III phenotype. Molecular analysis of four additional Turkish families with variable clinical expression of WS-I identified two missense mutations, one splice-site mutation, and one small insertion in the PAX3 gene. © 2003 Wiley-Liss, Inc.