Mutations in the PAX3 gene causing Waardenburg syndrome type 1 and type 2.
Waardenburg syndrome (WS) is a combination of deafness and pigmentary disturbances, normally inherited as an autosomal dominant trait. The pathology involves neural crest derivatives, but WS is heterogeneous clinically and genetically. Some type I WS families show linkage with markers on distal 2q and in three cases the disease has been attributed to mutations in the PAX3 gene. PAX3 encodes a paired domain, a highly conserved octapeptide and probably also a paired-type homeodomain. Here we describe a further three PAX3 mutations which cause WS; one alters the octapeptide motif plus the presumed homeodomain; a second alters all three elements and the third alters the paired box alone. The latter occurs in a family with probable type 2 WS, a clinical variant usually considered not to be allelic with type 1 WS.
Tassabehji
M
M
University Department of Medical Genetics, St Mary's Hospital, Manchester, UK.
Read
A P
AP
Newton
V E
VE
Patton
M
M
Gruss
P
P
Harris
R
R
Strachan
T
T
D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D010375:Pedigree; D016133:Polymerase Chain Reaction; D014157:Transcription Factors; D014849:Waardenburg Syndrome / Q000235:genetics*
D004268:DNA-Binding Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse; D004247:DNA