title: Missense mutation in the paired domain of PAX3 causes craniofacial-deafness-hand syndrome.
abstract: 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.
authors.affiliation: Department of Zoology, Michigan State University, East Lansing 48824, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Asher
authors.forename: A
authors.initials: A
authors.lastname: Sommer
authors.forename: R
authors.initials: R
authors.lastname: Morell
authors.forename: T B
authors.initials: TB
authors.lastname: Friedman
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D003638:Deafness; D005147:Facial Bones / Q000002:abnormalities*; D005260:Female; D016368:Frameshift Mutation; D006228:Hand Deformities, Congenital; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016415:Sequence Alignment; D017384:Sequence Deletion; D012886:Skull / Q000002:abnormalities*; D013577:Syndrome; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse