Unstable pre‐mutation may explain mosaic disease expression of incontinentia pigmenti in males

Abstract

Mosaic skin lesions following the lines of Blaschko are found in boys affected by incontinentia pigmenti (IP). 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.