Mutations in PAX1 may be associated with Klippel-Feil syndrome

• Published in: European journal of human genetics : EJHG Vol. 11; no. 6; pp. 468 - 474
• Main Authors: MCGAUGHRAN, J. M, OATES, A, DONNAI, D, READ, A. P, TASSABEHJI, M
• Format: Journal Article
• Language: English
• Published: Avenel, NJ Nature Publishing 01-06-2003; Nature Publishing Group
• Subjects: Base Sequence; Biological and medical sciences; Diseases of the osteoarticular system; DNA Mutational Analysis; DNA Primers; DNA-Binding Proteins - genetics; Genetic Testing; Humans; Klippel-Feil Syndrome - genetics; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical sciences; Molecular Sequence Data; Paired Box Transcription Factors; Polymorphism, Genetic; Transcription Factors - genetics; Human; Klippel Feil deformity; Pathogenesis; Diseases of the osteoarticular system; Dysostosis; Spine disease; Mutation; Genetic determinism; Syndrome
• ISSN: 1018-4813; 1476-5438
• DOI: 10.1038/sj.ejhg.5200987

Pax genes are a highly conserved family of developmental control genes that encode transcription factors. In vertebrates, Pax genes play a role in pattern formation during embryogenesis. Mutations in Pax genes have been associated with both spontaneous mouse mutants and congenital human diseases. The mouse Pax1 mutant phenotype undulated is characterised by vertebral segmentation defects reminiscent of the human disorder Klippel-Feil syndrome (KFS). To determine whether PAX1 haploinsufficiency plays a role in KFS, we have defined the gene structure of the human PAX1 gene and screened 63 KFS patients for mutations in this gene. Differences in the PAX1 sequence were detected in eight patients. Two patients had a silent change within the paired box that was also seen in 2/303 control chromosomes. The other variants were missense, silent or intronic changes not represented in the control panel tested. The significance of these results and the possible role of PAX1 in the pathogenesis of KFS are discussed.