Missense mutation in the paired domain of PAX3 causes craniofacial-deafness-hand syndrome

Hum Mutat. 1996;7(1):30-5. doi: 10.1002/(SICI)1098-1004(1996)7:1<30::AID-HUMU4>3.0.CO;2-T.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • DNA-Binding Proteins / genetics*
  • Deafness
  • Facial Bones / abnormalities*
  • Female
  • Frameshift Mutation
  • Hand Deformities, Congenital*
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation*
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Sequence Alignment
  • Sequence Deletion
  • Skull / abnormalities*
  • Syndrome
  • Transcription Factors*


  • DNA-Binding Proteins
  • PAX3 Transcription Factor
  • PAX3 protein, human
  • Paired Box Transcription Factors
  • Transcription Factors
  • Pax3 protein, mouse