Table 3.

Basic mechanisms of the genetic causes of XLID in female patients with skewing

Skewing		XLID
One-hit model	1. Mutation in XLID gene that escapes XCI and causes skewing (on Xa/Xi)
	2. Mutation in XLID gene with insufficient skewing to rescue complete phenotype
	3. Chance	Mutation in XLID gene that does not affect XCI (on Xa)
		Mutation in XLID gene that escapes XCI and does not affect XCI (on Xa/Xi)
Two-hit model	Mutation causing skewing (Xi)	Mutation in XLID gene (on Xa)
	Mutation causing skewing (Xi)	Mutation in XLID gene that causes escape (on Xa/Xi)
	Mutation in XCI machinery (on Xa/Xi)	Mutation in XLID gene (on Xa)
		Mutation in XLID gene that escapes XCI (on Xa/Xi)

Mechanisms relying on secondary skewing are shaded in grey and mechanisms caused by primary skewing are not highlighted. Xa = active X chromosome; Xi = inactive X chromosome.