caa a22 4500 397573731 CHVBK 20180308164848.0 cr unu---uuuuu 161202e199611 xx s 000 0 eng 10.1093/hmg/5.11.1777 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.11.1777 Selection Against Mutant Alleles in Blood Leukocytes is a Consistent Feature in Incontinentia Pigmenti Type 2 [Elektronische Daten] [Julia E. Parrish, Angela E. Scheuerle, Richard A. Lewis, Moise L. Levy, David L. 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 ∼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. © 1996 Oxford University Press Parrish Julia E. Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA aut Scheuerle Angela E. Division of Medical Genetics, Department of Pediatrics, University of Texas-Houston Medical School, Houston, TX 77030, USA aut Lewis Richard A. Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA aut Levy Moise L. Department of Dermatology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA aut Nelson David L. Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA aut Human Molecular Genetics Oxford University Press 5/11(1996-11), 1777-1783 0964-6906 5:11<1777 1996 5 hmg https://doi.org/10.1093/hmg/5.11.1777 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.11.1777 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Parrish Julia E. Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA aut NATIONALLICENCE 700 1- Scheuerle Angela E. Division of Medical Genetics, Department of Pediatrics, University of Texas-Houston Medical School, Houston, TX 77030, USA aut NATIONALLICENCE 700 1- Lewis Richard A. Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA aut NATIONALLICENCE 700 1- Levy Moise L. Department of Dermatology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA aut NATIONALLICENCE 700 1- Nelson David L. Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/11(1996-11), 1777-1783 0964-6906 5:11<1777 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford