PAX genes in human developmental anomalies

Pax genes encode the highly conserved 128 amino acid paired domain, first seen in the Drosophila paired gene. Humans and mice each have nine Pax genes, scattered across the genome. They are mostly expressed in the developing nervous system, with some specific expression in adults, and they control important aspects of cell growth and differentiation. Development is sensitive to Pax gene dosage. Loss of function mutations in PAX3 and PAX6 cause Waardenburg syndrome and aniridia, respectively, while a gain of function mutation in which PAX3 forms a chimaeric gene by fusion to the FKHR transcription factor causes the paediatric tumour alveolar rhabdomyosarcoma. Pax gene mutations are likely to underlie other developmental syndromes and cancers.