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PAX3 gene history
The paired box homeotic gene 3, or PAX3 gene encodes a DNA binding
transcription factor that is expressed during embryonic development.
In 1951, mutations of this gene were found to be linked to Waardenburg
Syndrome type I. This was done by Petrus J. Waardenburg.
Type II was discovered in 1971 by Arias, and type III was discovered in
1983 by Klein, who renamed this type Klein-Waardenburg syndrome.
It is an autosomal dominant disorder characterized by sensorineural hearing
loss, dystophia canthorum, and pigmentory abnormalities.
Jeremy Kohansimeh
Experimental Strategy
PCR amplification was used in the homologous mouse gene to clone the
intron between exons 2 and 3 of the PAX3 gene.
This intron was then used as a probe to determine the genes chromosomal
location, using DNA from somatic cell hybrids on a Southern blot.
Utilizing this strategy the PAX3 gene was found to be located at 2q35.
Conventional methods were used to obtain the DNA sequence .
Jeremy Kohansimeh
Gene Structure
The human PAX3 gene is comprised of 8 exons and 7 introns.
The wild type strain contains paired box domains; located on the 2nd,
3rd and 4th exons, an octapeptide motif on the 4th exon, and
homeobox domains; located on the 5th and 6th exons.
Jeremy Kohansimeh
Protein Structure
The PAX3 protein is comprised of extended, random-coil, beta-turn,
and alpha-helix regions.
Mutations in the amino acids of this protein can cause varying secondary
structures.
PAX3 is a transcription factor that regulates the expression of other genes by
binding to DNA.
Jeremy Kohansimeh
PAX3 Mutational Analysis
Mutations in the PAX3 gene include amino acid substitutions, premature
termination codons, small in-frame or out-of-frame deletions/ insertions, and
large segment chromosomal abnormalities.
The mutant genotype has no correlation with the phenotypic expression of
the syndrome.
Jeremy Kohansimeh
Works Consulted
Baldwin, Clinton T., Christopher F. Hoth, Roberto A. Macina, and Aubrey Milunksky. “Mutations in PAX3
that cause Waardenburg syndrome type I: ten new mutations and a review of the literature.”
American Journal of Medical Genetics 58 (1995): 115-122
Lalwani, Anil K., Anand N. Mhatre, Theresa B. San Augustin, and Edward R. Wilcox. “Genotype-phenotype
correlations in type I Waardenburg syndrome.” Laryngoscope 106 (1996): 895-903
Macina, Roberto A., Frederic G. Barr, Naomi Galili, and Harold C. Riethman. “Genomic organization of the
human PAX3 gene: DNA sequence analysis of the region disrupted in alveolar
rhabdomyosarcome.” Genomics 26 (1995): 1-8
Read, Andrew P., and Valerie E. Newton. “Waardenburg syndrome.” Journal of Medical Genetics 34 (1997)
656-665
Tassabehji, M., V.E. Newton, K.Leverton, K. Turnbull, E. Seemanova, J. Kunze, K. Sperling, T. Strachan and
A.P. Reed. “PAX3 gene structure and mutations: close analogies between Waardenburg
syndrome and the Splotch mouse.” Human Molecular Genetics 3 (1994): 1069-1074
Wilcox, Edward R., Marcelo N. Rivolta, Barbara Ploplis, Stephen B. Potterfand Jorgen Fex. “The PAX3
gene is mapped to human chromosome2 together with a highly informative CA dinucleotide
repeat.” Human Molecular Genetics 1 (1992): 215
Jeremy Kohansimeh