Expression of the disease on female carriers of X-linked lysosomal disorders: a brief review

Table 3 Relation between genic product properties, cellular selection, X-inactivation and phenotype of heterozygotes for X-linked diseases: the example of Fabry disease and MPS II (based on Dobyns et al., 2004 [48] and Dobyns, 2006 [53])

Type of gene product	Positive cellular selection (gene product causing early cell death)	Clinical Phenotype in Heterozygotes	Probably X-inactivation Pattern	Disease
Cell-autonomous	No	Normal	Random or skewed favorable to the normal allele	Fabry disease³
	No	Abnormal	Random or skewed unfavorable to the normal allele⁴	Fabry disease³
Non-cell-autonomous¹ or functionally non-autonomous²	No	Normal	Random or skewed favorable to the normal allele	MPS II
	No	Abnormal	Skewed favorable to the abnormal allele	MPS II

¹Non-autonomous gene products would include primarily secreted proteins; ²Functionally non-autonomous would include proteins expressed in non-clonal, multinucleated cells and small molecules that pass freely between cells; ³Athough the genic product of Fabry disease is non-cell autonomous, the hypothesis is that cross-correction capacity in this disease is low and, as a result, it is being classified in this table as cell-autonomous.⁴The phenotype can be modulated by the presence of a randomic X-inactivation, e.g., the phenotype is abnormal, and/or by an unfavourable skewed to the normal allele; then, a more severe phentoype is expected.

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