(last modified October 26, 2001)
In rare instances, females have been found which have a DMD or BMD phenotype. Theoretically, at a molecular level, several potential causes can be envisaged;
The most frequently identified cause detected so far is a (balanced) translocation disrupting the DMD-gene. As a consequence, the DMD-gene is split in two and joined with a segment of another chromosome (autosome) and no functional dystrophin can be produced. The believe is that on the derivative autosomal chromosome, the Xpter-Xp21.2 sequences become separated from the X-inactivation center at Xq13 and will not be silenced. In addition, when the derivative X-chromosome becomes inactivated, inactivation will spread into the autosomal sequences joined to the der(X)-chromosome, results in a silencing of these autosomal genes (expression is blocked). The resulting overall gross imbalance of expressed sequences is most likely a cell-lethal condition in early embryonic stages, resulting in selection against such cells. As a consequence, only cells where the normal X-chromosome is inactivated will survive. At the same time this means that only cells survive where the normal dystrophin gene is inactive, yielding a DMD-phenotype. Several studies have been published which describe female-DMD translocation cases. Some of these have been characterized in detail, including, mapping, cloning and even sequencing of the translocation breakpoints (for details see Translocations in the DMD-gene)
In other cases, manifesting carriers (DMD/BMD females) have been identified which have a non-random X-inactivation. In some cases the non-random X-inactivation was associated with monozygotic twinning (Richards, 1990), in other cases no obvious reason could be identified (Francke, 1989). Females carrying two mutated dystrophin genes have not been reported so far.
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