| | |  | | | | Record from Web of Science® | | | | | | |
| Revertant mosaicism: partial correction of a germ-line mutation in COL17A1 by a frame-restoring mutation |
|
|
| Author(s): Darling TN, Yee C, Bauer JW, Hintner H, Yancey KB |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 103 Issue: 10 Pages: 1371-1377 Published: MAY 1999 |
| Times Cited: 30 References: 28 |
| Abstract: Generalized atrophic benign epidermolysis bullosa is an autosomal recessive subepidermal blistering disease typified by null mutations in COL17A1. In 1 large kindred, affected individuals were homozygous for a 2-bp deletion in COL17A1, 4003delTC, which resulted in a downstream premature termination codon, nonsense-mediated mRNA decay, and abrogation of type XVII collagen synthesis. Interestingly, 1 of these patients, although phenotypically identical to her affected siblings, showed focal expression of type XVII collagen in epidermal basement membrane in a pattern suggestive of revertant mosaicism. When studies of randomly obtained epidermal, oromucosal, and peripheral blood cells failed to identify the genetic basis of this apparent mosaicism, microscopic subpopulations of potentially revertant epidermal cells (i.e., those overlying basement membrane containing type XVII collagen) were selectively isolated using laser capture microdissection. Analysis of DNA and RNA from these cells revealed a second mutation, 4080insGG, on 1 allele of COL17A1. This 2-bp insertion corrected the reading frame just proximal to the premature termination codon, countered nonsense-mediated mRNA decay, and allowed protein production by patient keratinocytes in vivo and in vitro. These studies elucidate the molecular basis of a novel form of revertant mosaicism in humans. |
| Document Type: Article |
| Language: English |
| Reprint Address: Darling, TN (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Room 12N238,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA |
Addresses:
1. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA
2. Gen Hosp, Dept Dermatol, A-5020 Salzburg, Austria |
| Publisher: AMER SOC CLINICAL INVESTIGATION INC, ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: 251VN |
| ISSN: 0021-9738 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |