Human Molecular Genetics, Vol 5, 1777-1783, Copyright © 1996 by Oxford University Press
JE Parrish, AE Scheuerle, RA Lewis, ML Levy and DL Nelson
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 approximately 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.
ARTICLES
Selection against mutant alleles in blood leukocytes is a consistent feature in Incontinentia Pigmenti type 2
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
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