with several autoimmune diseases, including autoimmune thyroid disease (ATD) and scleroderma. Autoimmune thyroid disease is a disease involving the thyroid gland. The immune system of those who have the condition recognize the thyroid as foreign and attack it, causing it to atrophy. Women have a predisposition towards the condition, and research indicates that this might in part be due to skewed X-inactivation. It was discovered that when twins with the disease were examined, the prevalence of skewing was above 30% as compared to 11% in the control group of wild type women, indicating that X-chromosome skewing could possibly be involved in the cause of the condition. Similar results have also been witnessed in scleroderma, which involves hardening of the skin and inner organs. Skewing levels were found in 64% of informative patients, as compared to only 8% of the control group, also indicating a strong correlation and possible cause. The mechanism behind both conditions is unclear at this time. Autism Higher levels of skewed X chromosome inactivation have been correlated with cases of autism in women. 33% of autistic women in a study had extreme levels of skewing, with only 11% of the wildtype control having extreme levels of skewing. The study also revealed that the mothers of the autistic daughters with skewing also had significant levels of skewing, indicating a higher level of heritability as compared to the wild type population. The reason behind this is currently unknown, as no mutations in the Xist promoter were detected. Klinefelter syndrome Klinefelter 47,XXY and 48,XXYY patients were found to have significantly skewed X-chromosome levels in 31% of the patients examined, with researchers predicting that this skewing might be responsible for the mental deficiencies and abnormalities present. Different forms of the disease also showed preferential activation towards either the maternal or paternal X chromosome. This might indicate that parent-of-origin effects such as imprinting might be involved with the X-chromosome skewing. Metabolism X-linked glycogen storage disease (GSD IXa) is a metabolic disorder typically only seen in males because of the X-linked inheritance pattern. Since women are mosaic models when it comes to gene expression, they tend to mask X-linked mutations by using the other X to compensate. Skewed X-inactivation resulting in the expression of the defective X chromosome can cause X-linked mutations to be expressed in women. The problem occurring in IXa is a defect in phosphorylase b kinase (PHK). PHK activates glycogen