Skewed X-inactivation

Skewed X-inactivation (lyonization)—A process by which inactivation of the X chromosome is not random. 

Richards CS, Watkins SC, Hoffman EP, Schneider NR, Milsark IW, Katz KS, et al. Skewed X inactivation... 

Yoshioka M, Yorifuji T, Mituyoshi I. Skewed X inactivation in manifesting carriers of Duchenne muscular dystrophy. Clin Genet 1998 52 102-7. 

Nomura Y, Onigata K, Nagashima T et al (1997) Detection of skewed X-inactivation in two female carriers of vasopressin type 2 receptor gene mutation. J Clin Endocrinol Metab 82 3434-3437... 

Valleix S, Vinciguerra C, Lavergne JM, Leuer M, Delpech M, Negrier C. Skewed X-chromosome inactivation in monochorionic diamniotic twin sisters results in severe and mild hemophilia A. Blood 2002 100 3034-6. 

X-linked recessive inheritance in females is impacted by a phenomenon known as X-inactivation or lyonization. A female s sex chromosomal constitntion is XX a male s sex chromosome constitntion is in XY. In females, a recessive disease mntation on one X chromosome should not resnlt in disease if the corresponding gene on the other X chromosome is normal. In actuality, the situation is more complicated. In females, one of the X chromosomes in each cell is randomly inactivated, a process known as X-inactivation. This is done to compensate for the donble state of X chromosomes in females relative to males. If the inactivation pattern is skewed so that the majority of X chromosomes with the normal gene are inactivated, the individual may be affected. The greater the skewed inactivation pattern, the more severe the disease. Becanse of this, the clinical phenotype of females with an X-linked recessive disorder, snch as ornithine transcarbamylase (OTC) deficiency, can range from nnaffected to severely affected. 

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