PT  - JOURNAL ARTICLE
AU  - Cardoso, Carlos
AU  - Lutz, Yves
AU  - Mignon, Cecile
AU  - Compe, Emmanuel
AU  - Depetris, Danielle
AU  - Mattei, Marie-Geneviève
AU  - Fontes, Michel
AU  - Colleaux, Laurence
TI  - <em>ATR-X</em> mutations cause impaired nuclear location and altered DNA binding properties of the XNP/ATR-X protein
AID  - 10.1136/jmg.37.10.746
DP  - 2000 Oct 01
TA  - Journal of Medical Genetics
PG  - 746--751
VI  - 37
IP  - 10
4099  - http://jmg.bmj.com/content/37/10/746.short
4100  - http://jmg.bmj.com/content/37/10/746.full
SO  - J Med Genet2000 Oct 01; 37
AB  - Mutations in the XNP/ATR-X gene, located in Xq13.3, are associated with several X linked mental retardation syndromes, the best known being α thalassaemia with mental retardation (ATR-X). The XNP/ATR-X protein belongs to the family of SWI/SNF DNA helicases and contains three C2-C2 type zinc fingers of unknown function. Previous studies have shown that 65% of mutations ofXNP have been found within the zinc finger domain (encoded by exons 7, 8, and the beginning of exon 9) while 35% of the mutations have been found in the helicase domain extending over 3 kb at the C-terminus of the protein. Although different types of mutations have been identified, no specific genotype-phenotype correlation has been found, suggesting that gene alteration leads to a loss of function irrespective of mutation type. Our aims were to understand the function of the XNP/ATR-X protein better, with specific attention to the functional consequences of mutations to the zinc finger domain. We used monoclonal antibodies directed against the XNP/ATR-X protein and performed immunocytochemical and western blot analyses, which showed altered or absentXNP/ATR-X expression in cells of affected patients. In addition, we used in vitro experiments to show that the zinc finger domain can mediate double stranded DNA binding and found that the DNA binding capacity of mutant forms in ATR-X patients is severely reduced. These data provide insights into the understanding of the functional significance of XNP/ATR-Xmutations.