Missense mutation in the paired domain of PAX3 causes craniofacial-deafness-hand syndrome
Article first published online: 7 JAN 1999
Copyright © 1996 Wiley-Liss, Inc.
Volume 7, Issue 1, pages 30–35, 1996
How to Cite
Asher, J. H., Sommer, A., Morell, R. and Friedman, T. B. (1996), Missense mutation in the paired domain of PAX3 causes craniofacial-deafness-hand syndrome. Hum. Mutat., 7: 30–35. doi: 10.1002/(SICI)1098-1004(1996)7:1<30::AID-HUMU4>3.0.CO;2-T
- Issue published online: 7 JAN 1999
- Article first published online: 7 JAN 1999
- Manuscript Accepted: 10 JAN 1995
- Manuscript Received: 14 DEC 1994
- Nat'l Institute of Deafness and Communication Disorders. Grant Number: R01DC 01160
- Craniofacial dysmorphology;
- PAX3 mutation;
- Paired domain mutation
Craniofacial-deafness-hand syndrome (MIM 122880) is inherited as an autosomal dominant mutation characterized by the absence or hypoplasia of the nasal bones, profound sensorineural deafness, a small and short nose with slitlike nares, hypertelorism, short palpebral fissures, and limited movement at the wrist and ulnar deviations of the fingers. In a family of three affected individuals with this syndrome, a mother and two children, a missense mutation (Asn47Lys) in the paired domain of PAX3 was initially detected by SSCP analysis. PCR amplification using an oligonucleotide with a terminal 3′-residue match for the C-to-G transversion in codon 47 showed the presence of this mutation in the DNA from all affected members. The DNA from unaffected members were refractory to PCR amplification with the mutation-specific oligonucleotide but did amplify a control primer pair in the same PCR reaction tube. A previously described missense mutation in this same codon (Asn47His) is associated with Waardenburg syndrome type 3 (Hoth et al., 1993). Substitution of a basic amino acid for asparagine at residue 47, conserved in all known murine Pax and human PAX genes, appears to have a more drastic effect on the phenotype than missense, frameshift and deletion mutations of PAX3 that cause Waardenburg syndrome type 1. © 1996 Wiley-Liss, Inc.