methylation of homocysteine. ATR association can be separated into two groups. ATR-16 syndrome patients have a 1-2Mb deletion on the top of the chromosome 16 p-arm and are associated with a Mendelian inheritance of a-thalassemia. ATR-X syndrome patients have no deletion in chromosome 16, a-thalassemia is rare, and this syndrome is consistent with X-linked recessive inheritance. However, both groups have similar phenotypes. The phenotypes resulting from ATR-X are due to skewed x-inactivation. When X-inactivation occurs randomly, half of the cells in the carrier female would contain the abnormality. When X-inactivation is skewed, more than 50% of one X chromosome are becoming inactive, and if that X-chromosome is passed to a male, they will have a higher percent of heterochromatin. The ATR-X locus spans the control center Xist, which regulates X-inactivation. When there is a XH2 mutation in the ATR-X locus, this indicates Xist to inactivate the chromosome increasing the amount of heterochromatin in males. Epigenetics is also present among transcriptional regulators. ATR-X is caused by XH2 mutations in the region Xq13.3, and XH2 belongs to the subgroup SNF2. This group is important for regulating the transcription of the alpha genes. Diagnosis If ATR-X is suspected based on symptoms, diagnosis can be done via Genome testing. If the results are conclusive with Atr-x syndrome, female members of the same family will often be asked to partake in genome testing to see if anyone else in the family may possess this gene. Notes References Further reading GeneReviews/NCBI/NIH/UW entry on Alpha-Thalassemia X-Linked Mental Retardation Syndrome; ATRX Syndrome; Alpha Thalassemia/Mental Retardation, X-Linked; XLMR-Hypotonic Face Syndrome OMIM entries on Alpha-Thalassemia X-Linked Mental Retardation Syndrome External links Genetic diseases and disorders Syndromes