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Bart's Syndrome: Ultrastructure and Genetic Linkage

Bart's Syndrome: Ultrastructure and Genetic Linkage Abstract Background and Design: Bart's syndrome, originally described in a large family in 1966, consists of congenital localized absence of skin, blistering, and associated nail abnormalities. Since then, several descriptions of patients with similar clinical findings have suggested that this syndrome may represent any of the three subtypes of epidermolysis bullosa: epidermal, junctional, or dermal. Because no histologic or ultrastructural studies were done in Bart's kindred, and neither immunohistologic nor genetic linkage technology was available at that time, classification of the syndrome has been unclear. We report the findings of clinical, ultrastructural, immunohistologic, and genetic linkage studies of the original kindred and their descendants. We contacted original family members and their descendants by telephone and questionnaire. Skin biopsy specimens adjacent to blisters were obtained for ultrastructural and immunochemical analysis. Blood samples were drawn from affected members and their spouses and children for genetic linkage studies. Results: The clinical findings seen in the descendants of the original family with Bart's syndrome were similar to those described in 1966. We did, however, detect persistence of blistering into adult life and mild atrophic scarring and milia formation at sites of blistering in some family members, a finding not noted in the original study. Hypertrophic scarring and albopapuloid lesions were not detected. Ultrastructural analysis of skin from affected family members showed poorly formed anchoring fibrils and cleavage below the lamina densa. Immunohistochemical staining localized type IV collagen at the roof of blistered skin. Staining for type VII collagen was found to have a normal distribution in nonblistered skin. Genetic linkage studies mapped the gene for the disease in this family to chromosome 3p at or near the site of the gene encoding type VII collagen. Conclusion: Bart's syndrome is a subtype of dominantly inherited dystrophic epidermolysis bullosa.(Arch Dermatol. 1995;131:663-668) References 1. Bart BJ, Gorlin RJ, Anderson VE, Lynch FW. Congenital localized absence of skin and associated abnormalities resembling epidermolysis bullosa: a new syndrome . Arch Dermatol. 1966;93:296-304.Crossref 2. Bonifas JM, Rothman AL, Epstein EH Jr. Epidermolysis bullosa simplex: evidence in two families for keratin gene abnormalities . Science. 1991;254:1202-1205.Crossref 3. Hall JM, Friedman L, Guenther C, et al. Closing in on a breast cancer gene on chromosome 17q . Am J Hum Genet. 1992;50:1235-1242. 4. Christiano AM, Chung-Honet LC, Hovnanian A, Uitto J. PCR-based detection of two exonic polymorphisms in the human type VII collagen gene (COL7A1) at 3p21.1 . Genomics. 1992;14:827-828.Crossref 5. Ott J. Analysis of Human Genetic Linkage . rev ed. Baltimore, Md: Johns Hopkins University Press; 1992. 6. Olaisen B, Gedde-Dahl T Jr. GPT-epidermolysis bullosa simplex (EBS Ogna) linkage in man . Hum Hered. 1973;23:189-196.Crossref 7. Weissenbach J, Gyapay G, Dib C, et al. A second-generation linkage map of the human genome . Nature. 1992;359:794-801.Crossref 8. Frieden IJ. Aplasia cutis congenita . J Am Acad Dermatol. 1986;14:646-660.Crossref 9. Fine JD, Bauer EA, Briggaman RA, et al. Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa . J Am Acad Dermatol. 1991; 24:119-135.Crossref 10. Epstein EH Jr. Molecular genetics of epidermolysis bullosa . Science. 1992; 256:799-803.Crossref 11. Marinkovich MP. The molecular genetics of basement membrane diseases . Arch Dermatol. 1993;129:1557-1565.Crossref 12. Hovnanian A. The molecular genetics of dystrophic epidermolysis bullosa . Arch Dermatol. 1993;129:1566-1570.Crossref 13. Leigh IM, Lane EB. Mutations in the genes for epidermal keratins in epidermolysis bullosa and epidermolytic hyperkeratosis . Arch Dermatol. 1993;129: 1571-1577.Crossref 14. Smith LT. Ultrastructural findings in epidermolysis bullosa . Arch Dermatol. 1993; 129:1578-1584.Crossref 15. Bart BJ. Epidermolysis bullosa and congenital localized absence of skin . Arch Dermatol. 1970;101:78-81.Crossref 16. Smith SZ, Cram DL. A mechanobullous disease of the newborn: Bart's syndrome . Arch Dermatol. 1978;114:81-84.Crossref 17. Kanzler MH, Smoller B, Woodley DT. Congenital localized absence of the skin as a manifestation of epidermolysis bullosa . Arch Dermatol. 1992;128:1087-1090.Crossref 18. Skoven I, Drzewiecki KT. Congenital localized skin defect and epidermolysis bullosa hereditaria letalis . Acta Derm Venereol (Stockh) . 1979;59:533-537. 19. Wojnarowska FT, Eady RAJ, Wells RS. Dystrophic epidermolysis bullosa presenting with congenital localized absence of skin: report of four cases . Br J Dermatol. 1983; 108:477-483.Crossref 20. Bouwes Bavinck JN, Van Haeringen A, Ruiter D, Van der Schroeff JG. Autosomal dominant epidermolysis bullosa dystrophica . Clin Genet. 1987;31:416-424.Crossref 21. Joensen HD. Epidermolysis bullosa dystrophica dominans in two families in the Faroe Islands . Acta Derm Venereol (Stockh) . 1973;53:53-60. 22. Butler DF, Berger TG, James WD, Smith TL, Stanley JR, Rodman OG. Bart's syndrome: microscopic, ultrastructural and immunofluorescent mapping features . Pediatr Dermatol. 1986;3:113-118.Crossref 23. Gruis NA, Bouwes Bavinck JN, Steijlen PM, et al. Genetic linkage between the collagen VII (COL7A1) gene and the autosomal dominant form of dystrophic epidermolysis bullosa in two Dutch kindreds . J Invest Dermatol. 1992;99:528-530.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Dermatology American Medical Association

Bart's Syndrome: Ultrastructure and Genetic Linkage

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Publisher
American Medical Association
Copyright
Copyright © 1995 American Medical Association. All Rights Reserved.
ISSN
0003-987X
eISSN
1538-3652
DOI
10.1001/archderm.1995.01690180037006
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See Article on Publisher Site

Abstract

Abstract Background and Design: Bart's syndrome, originally described in a large family in 1966, consists of congenital localized absence of skin, blistering, and associated nail abnormalities. Since then, several descriptions of patients with similar clinical findings have suggested that this syndrome may represent any of the three subtypes of epidermolysis bullosa: epidermal, junctional, or dermal. Because no histologic or ultrastructural studies were done in Bart's kindred, and neither immunohistologic nor genetic linkage technology was available at that time, classification of the syndrome has been unclear. We report the findings of clinical, ultrastructural, immunohistologic, and genetic linkage studies of the original kindred and their descendants. We contacted original family members and their descendants by telephone and questionnaire. Skin biopsy specimens adjacent to blisters were obtained for ultrastructural and immunochemical analysis. Blood samples were drawn from affected members and their spouses and children for genetic linkage studies. Results: The clinical findings seen in the descendants of the original family with Bart's syndrome were similar to those described in 1966. We did, however, detect persistence of blistering into adult life and mild atrophic scarring and milia formation at sites of blistering in some family members, a finding not noted in the original study. Hypertrophic scarring and albopapuloid lesions were not detected. Ultrastructural analysis of skin from affected family members showed poorly formed anchoring fibrils and cleavage below the lamina densa. Immunohistochemical staining localized type IV collagen at the roof of blistered skin. Staining for type VII collagen was found to have a normal distribution in nonblistered skin. Genetic linkage studies mapped the gene for the disease in this family to chromosome 3p at or near the site of the gene encoding type VII collagen. Conclusion: Bart's syndrome is a subtype of dominantly inherited dystrophic epidermolysis bullosa.(Arch Dermatol. 1995;131:663-668) References 1. Bart BJ, Gorlin RJ, Anderson VE, Lynch FW. Congenital localized absence of skin and associated abnormalities resembling epidermolysis bullosa: a new syndrome . Arch Dermatol. 1966;93:296-304.Crossref 2. Bonifas JM, Rothman AL, Epstein EH Jr. Epidermolysis bullosa simplex: evidence in two families for keratin gene abnormalities . Science. 1991;254:1202-1205.Crossref 3. Hall JM, Friedman L, Guenther C, et al. Closing in on a breast cancer gene on chromosome 17q . Am J Hum Genet. 1992;50:1235-1242. 4. Christiano AM, Chung-Honet LC, Hovnanian A, Uitto J. PCR-based detection of two exonic polymorphisms in the human type VII collagen gene (COL7A1) at 3p21.1 . Genomics. 1992;14:827-828.Crossref 5. Ott J. Analysis of Human Genetic Linkage . rev ed. Baltimore, Md: Johns Hopkins University Press; 1992. 6. Olaisen B, Gedde-Dahl T Jr. GPT-epidermolysis bullosa simplex (EBS Ogna) linkage in man . Hum Hered. 1973;23:189-196.Crossref 7. Weissenbach J, Gyapay G, Dib C, et al. A second-generation linkage map of the human genome . Nature. 1992;359:794-801.Crossref 8. Frieden IJ. Aplasia cutis congenita . J Am Acad Dermatol. 1986;14:646-660.Crossref 9. Fine JD, Bauer EA, Briggaman RA, et al. Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa . J Am Acad Dermatol. 1991; 24:119-135.Crossref 10. Epstein EH Jr. Molecular genetics of epidermolysis bullosa . Science. 1992; 256:799-803.Crossref 11. Marinkovich MP. The molecular genetics of basement membrane diseases . Arch Dermatol. 1993;129:1557-1565.Crossref 12. Hovnanian A. The molecular genetics of dystrophic epidermolysis bullosa . Arch Dermatol. 1993;129:1566-1570.Crossref 13. Leigh IM, Lane EB. Mutations in the genes for epidermal keratins in epidermolysis bullosa and epidermolytic hyperkeratosis . Arch Dermatol. 1993;129: 1571-1577.Crossref 14. Smith LT. Ultrastructural findings in epidermolysis bullosa . Arch Dermatol. 1993; 129:1578-1584.Crossref 15. Bart BJ. Epidermolysis bullosa and congenital localized absence of skin . Arch Dermatol. 1970;101:78-81.Crossref 16. Smith SZ, Cram DL. A mechanobullous disease of the newborn: Bart's syndrome . Arch Dermatol. 1978;114:81-84.Crossref 17. Kanzler MH, Smoller B, Woodley DT. Congenital localized absence of the skin as a manifestation of epidermolysis bullosa . Arch Dermatol. 1992;128:1087-1090.Crossref 18. Skoven I, Drzewiecki KT. Congenital localized skin defect and epidermolysis bullosa hereditaria letalis . Acta Derm Venereol (Stockh) . 1979;59:533-537. 19. Wojnarowska FT, Eady RAJ, Wells RS. Dystrophic epidermolysis bullosa presenting with congenital localized absence of skin: report of four cases . Br J Dermatol. 1983; 108:477-483.Crossref 20. Bouwes Bavinck JN, Van Haeringen A, Ruiter D, Van der Schroeff JG. Autosomal dominant epidermolysis bullosa dystrophica . Clin Genet. 1987;31:416-424.Crossref 21. Joensen HD. Epidermolysis bullosa dystrophica dominans in two families in the Faroe Islands . Acta Derm Venereol (Stockh) . 1973;53:53-60. 22. Butler DF, Berger TG, James WD, Smith TL, Stanley JR, Rodman OG. Bart's syndrome: microscopic, ultrastructural and immunofluorescent mapping features . Pediatr Dermatol. 1986;3:113-118.Crossref 23. Gruis NA, Bouwes Bavinck JN, Steijlen PM, et al. Genetic linkage between the collagen VII (COL7A1) gene and the autosomal dominant form of dystrophic epidermolysis bullosa in two Dutch kindreds . J Invest Dermatol. 1992;99:528-530.Crossref

Journal

Archives of DermatologyAmerican Medical Association

Published: Jun 1, 1995

References