Selection against mutant alleles in blood leukocytes is a consistent feature in Incontinentia Pigmenti Type 2

Julia E. Parrish, Angela E. Scheuerle, Richard A. Lewis, Moise L. Levy, David L. Nelson

Research output: Contribution to journalArticlepeer-review

93 Scopus citations


Incontinentia Pigmenti 2 (IP2) is an X-linked dominant disorder with male lethality. Affected females display a characteristic skin eruption that evolves through four classic stages, frequently accompanied by dental and retinal abnormalities. Non-random (skewed) X-inactivation in peripheral blood leukocytes and in fibroblasts has been observed in females with IP2; however, sample sizes have been small and methods of analysis varied. We have examined X-inactivation in a large group of multigenerational IP2 families, in smaller families, and in isolated cases. Ninety-eight percent of affected females in multigenerational IP2 pedigrees show completely skewed patterns of X-inactivation, while only ~10% of a normal control population is skewed. Results both in small families and in new mutation cases with subsequent segregation consistent with Xq28 linkage are similar. Isolated cases show a lower percentage (85%) of skewed affected individuals; this difference may be due to inaccurate clinical ascertainment. The parent of origin of new mutations could be determined in 15 families; paternal new mutations were twice as common as maternal. Fibroblast subclones from a biopsy at the boundary of a skin lesion in a newborn IP2 patient were isolated, and clones with either one or the other X active were identified. demonstrating that cells with the active disease-bearing X chromosome are still present in stage I skin lesions.

Original languageEnglish (US)
Pages (from-to)1777-1783
Number of pages7
JournalHuman molecular genetics
Issue number11
StatePublished - Nov 1996

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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