A new detection method for ATRX gene mutations using a mismatch-specific endonuclease.

X-linked alpha-thalassemia/mental retardation syndrome (ATR-X, OMIM 301040) is a syndromic form of X-linked mental retardation (XLMR). It is caused by a mutation in the ATRX gene, which is also involved in other syndromic forms of XLMR as well as in non-syndromic XLMR, both in males and in females. To analyze the full range of disease-causing mutations for genetic counseling and to establish phenotype-genotype correlations, we have established a new screening method for mutations in the ATRX gene, which uses mismatch-specific endonuclease. We applied this method to confirm 13 known mutations in our patients, some of which have been difficult to be demonstrated by conventional denaturing high-performance liquid chromatography. Furthermore, we found four additional mutations in four ATR-X patients whose clinical diagnosis had not been confirmed at the molecular level. In this method, experimental conditions do not need to be altered depending on mutation sites, and it should be the alternative method for mutation screening.