Journal Article

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 and David L. Nelson

in Human Molecular Genetics

Volume 5, issue 11, pages 1777-1783
Published in print November 1996 | ISSN: 0964-6906
e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/5.11.1777
Selection Against Mutant Alleles in Blood Leukocytes is a Consistent Feature in Incontinentia Pigmenti Type 2

Show Summary Details

Preview

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. Fibro-blast 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.

Journal Article.  3963 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.