UNSTABLE PRE-MUTATION MAY EXPLAIN MOSAIC DISEASE EXPRESSION OF INCONTINENTIA PIGMENTI IN MALES

Mosaic skin lesions following the lines of Blaschko are found in boys affected by incontinentia pigmenti (IF). For an X-linked gene defect, this is rather surprising. To explain the mosaic disease expression of IP in males, we propose that the disease is caused by an unstable pre-mutation, which normally remains silent in males during early embryogenesis. Occasionally ''silencing'' is incomplete and gives rise to clinical manifest IP reflecting a mosaic state of alleles with the full and the pre-mutation in the same patient. This model can account for mother-to-son transmission of IP and for disparate phenotypes in monozygotic female twins. (C) 1994 Wiley-Liss, Inc.