PAX3 is a gene within the PAX family, a group of transcription factors consisting of proteins binding to DNA sequences to control gene transcription. Pax3 is important in embryonic development because Pax3 is active in neural crest cells. In conjunction with Msx1, Pax3 guides the expression of Snail1 and Snail2 down-regulating adhesion molecules. This allows neural crest cells to become mesenchymal cells that migrate throughout the body and become bones and muscles around the face, the parasympathetic nervous system, and other structural components. As a result, mutations within Pax3 generally result in developmental malformations because neural crest cells cannot move to the necessary parts of the body to complete their function. Craniofacial-deafness-hand syndrome is an example of an autosomal dominant disease resulting from a missense mutation in exon2 of Pax3. This mutation results in replacing the amino acid asparagine with lysine, inhibiting the Pax3 protein from binding to the necessary DNA. Craniofacial-deafness-hand syndrome has distinctive symptoms, such as an underdeveloped nasal bone, a small mouth and upper-jaw, pursed lips, and wide spaced eyes with narrowed eye openings. Hearing loss and deformities in hand muscles are common. Hand abnormalities typically present themselves as angled and bent fingers. Depending on the severity, finger and hand movement can be limited. Despite these physical malformations, individuals have normal intelligence and an active life. Diagnosis involves genotyping and collaborative efforts from orthopedists, pediatricians, and ophthalmologists. While there are knockout models developed for Pax3, they focused on cancers rather than this syndrome.
PAX3 is a gene that belongs to the paired box (PAX) family of transcription factors. This gene was formerly known as splotch. PAX3 has been identified with ear, eye and facial development. Mutations in it can cause Waardenburg syndrome types 1 and 3. It is expressed in early embryonic phases in dermatomyotome of paraxial mesoderm which it helps to demarcate. In that way PAX3 contributes to early striated muscle development since all myoblasts are derived from dermatomyotome of paraxial mesoderm.
A PAX3/FKHRfusion gene is often associated with the alveolar type of rhabdomyosarcoma, a kind of cancer arisen from striated muscle cells. Translocation between chromosomes 2 & 13 produce fusion protein PAX3/FKHR which serves as a tumor marker in this type of RMS.Also in ARMS expressing PAX3/FKHR increased risk of metastasis to bone marrow and hence increased rate of failure and death were seen.
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