Hereditary benign intraepithelial dyskeratosis: Report of two cases with prominent oral lesions.

Hereditary benign intraepithelial dyskeratosis is a rare autosomal dominant disorder of the oral and ocular mucosa initially described in the Haliwa-Saponi Native American tribe of North Carolina. We describe 2 sisters with the characteristic oral and ocular findings. This entity should be distinguished from several other diseases that cause white lesions in the mouth including white sponge nevus.

Additional glomangioma families link to chromosome 1p: no evidence for genetic heterogeneity.

Venous malformations are a common abnormality of the vasculature that may occur sporadically or, more rarely, as an autosomal dominant trait. One familial form of venous malformations has previously been linked to chromosome 9p. Mutations in the gene encoding Tie2, an endothelial specific receptor tyrosine kinase, have been identified in four different families. Glomangiomas are a subtype of venous malformations with glomus cell involvement. These cutaneous lesions can be inherited as an autosomal dominant disease with reduced penetrance and variable expressivity. We present evidence of linkage to chromosome 1p21-1p22 using four new glomangioma families, with a combined maximum two-point lod score of 7.32 at marker D1S2804. Markers D1S2129 and D1S2881 define the 24-cM linkage interval determined by recombination within affected individuals. A recent report also showed linkage of the glomangioma locus to chromosome 1p. A total of 9 families now map to this region, suggesting a decreased likelihood of locus heterogenity in familial glomangiomas. Investigation of candidate genes within the interval should provide new insights into lesion formation in inherited venous malformations.

Low-copy-number human transgene is recognized as an X inactivation center in mouse ES cells, but fails to induce cis-inactivation in chimeric mice.

X chromosome inactivation is initiated from a segment of the mammalian X chromosome called the X inactivation center. Transgenes from this region of the murine X chromosome are providing the means to identify the DNA needed for cis inactivation in mice. We recently showed that chimeric mice carrying transgenes from the human X inactivation center (XIC) region also provide a functional assay for human XIC activity; approximately 6 copies of a 480-kb human transgene (ES-10) were sufficient to initiate random X inactivation in cells of male chimeric mice (Migeon et al., 1999, Genomics, 59, 113-121). Now, we report studies of another human transgene (ES-5), which contains less than 300 kb of the human XIC region on Xq13.2 including an intact XIST locus and which has inserted in one or two copies into mouse chromosome 6. The ES-5 transgene is recognized as an X inactivation center in mouse embryonic stem cells, but is not sufficient to induce random X inactivation in somatic cells of highly chimeric mice. Human transgenes in chimeric mice provide a means to uncouple the key steps in this complex pathway and facilitate the search for essential components of the human XIC region.

Human X inactivation center induces random X chromosome inactivation in male transgenic mice.

X chromosome inactivation is the means to downregulate the transcriptional output of X chromosomes in female mammals. Essential DNA from the murine X inactivation center (Xic) has been identified by introducing it into male embryonic stem (ES) cells. To identify the essential sequences on human X chromosomes, we transfected male mouse ES cells with a YAC transgene containing 480 kb of the putative human X inactivation center (XIC). Despite little DNA sequence conservation, the human transgene is recognized as a second Xic in these XY mouse cells and induces random inactivation in chimeric mice derived from these cells. Inactivation is extensive on the X chromosome, but more localized on chromosome 11 carrying the transgene, demonstrating that initial inactivation and spreading of inactivation signals along the chromosome are independent events. Our results show for the first time that the DNA included in the human XIC transgene is sufficient to initiate random X inactivation, even in cells of another species. Interspecies XIC trangenes should facilitate further investigation of this process in humans and other mammals.