0
December 1993, Vol 129, No. 12 >
Article | December 1993

The Molecular Genetics of Dystrophic Epidermolysis Bullosa

Alain Hovnanian, MD; Angela M. Christiano, PhD; Jovni Vitto, MD, PhD
[+] Author Affiliations

Laboratoire de Biochimie et Génétique Moléculaire INSERM U. 91 Hôpital Henri Mondor 51 Av du Maréchal de Lattre de Tassigny 94010 Créteil, France; Department of Dermatology and Department of Biochemistry and Molecular Dermatology Jefferson Medical College Thomas Jefferson University Philadelphia, PA 19107


Arch Dermatol. 1993;129(12):1566-1570. doi:10.1001/archderm.1993.04540010044005
Text Size: A A A
Published online
Article
References
Comments

EPIDERMOLYSIS BULLOSA (EB) is a heterogeneous group of inherited skin diseases characterized by blistering of the skin and mucous membranes after minor trauma.1-3 The genes responsible for the three groups of EB (EB simplex, junctional EB, and dystrophic EB [DEB]) have recently been identified, and some molecular defects within these genes have been characterized.4,5 Specifically, EB simplex has been shown to arise from mutations in the keratin 5 and 14 genes6-10; the genes encoding nicein/kalinin/epiligrin are the candidate genes in junctional EB11; and both dominant and recessive forms of DEB (DDEB and RDEB, respectively) have been closely linked to the type VII collagen gene (COL7A1)12-16 that encodes the major component of anchoring fibrils (AFs).17,18 Biochemistry and molecular biology of basement membrane zone components involved in human diseases have been reviewed by Marinkovich19 in this issue of the Archives. This editorial focuses on the

REFERENCES

1 +
Gedde-Dahl TJ, Anton-Lamprecht I.  Epidermolysis bullosa . In: Rimoin DL, ed. Principles and Practice of Medical Genetics . New York, NY: Churchill Livingstone; 1990;:855-876.
2 +
Fine JD, Bauer EA, Briggaman RA, et al.  Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa: a consensus report by the Subcommittee on Diagnosis and Classification of the National Epidermolysis Bullosa Registry . J Am Acad Dermatol . 1991;;24:119-135.
3 +
Lin AN, Carter DM. Epidermolysis Bullosa: Basic and Clinical Aspects . New York, NY: Springer-Verlag NY Inc; 1992;.
4 +
Epstein EH Jr.  Molecular genetics of epidermolysis bullosa . Science . 1992;; 256:799-803.
5 +
Fuchs E.  Genetic skin disorders of keratin . J Invest Dermatol . 1992;;99:671674.
6 +
Bonifas JM, Rothman AL, Epstein EH Jr.  Epidermolysis bullosa simplex: evidence in two families for keratin gene abnormalities . Science . 1991;;254:1202-1205.
7 +
Coulombe PA, Hutton ME, Letai A, Hebert A, Paller AS, Fuchs E.  Point mutations in human keratin 14 genes of epidermolysis bullosa simplex patients: genetic and functional analyses . Cell . 1991;;66:1301-1311.
8 +
Lane EB, Rugg EL, Navsaria H, et al.  A mutation in the conserved helix termination peptide of keratin 5 in hereditary skin blistering . Nature . 1992;;356:244-246.
9 +
Dong W, Ryynänen M, Uitto J.  Identification of a leucine-to-proline mutation in the keratin 5 gene in a family with the generalized Köbner type of epidermolysis bullosa simplex . Hum Mut . 1993;;2:94-102.
10 +
Hovnanian A, Pollack E, Hilal L, et al.  A missense mutation in the rod domain of keratin 14 associated with recessive epidermolysis bullosa simplex . Nature Genet . 1993;;3:327-332.
11 +
Meneguzzi G, Marinkovich MP, Aberdam D, Pisani A, Burgeson R, Ortonne JP.  Kalinin is abnormally expressed in epithelial basement membranes of Herlitz's junctional epidermolysis bullosa patients . Exp Dermatol . 1993;;1:221-229.
12 +
Ryynänen M, Knowlton RG, Parente MG, Chung LC, Chu ML, Uitto J.  Human type VII collagen: genetic linkage of the gene (COL7A1) on chromosome 3 to dominant dystrophic epidermolysis bullosa . Am J Hum Genet . 1991;;49:797-803.
13 +
Ryynänen M, Ryynänen J, Sollberg S, lozzo RV, Knowlton RG, Uitto J.  Genetic linkage of type VII collagen (COL7A1) to dominant dystrophic epidermolysis bullosa in families with abnormal anchoring fibrils . J Clin Invest . 1992;;89:974-980.
14 +
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.
15 +
Al-Imara L, Richards AJ, Eady RAJ, Leigh IM, Farrall M, Pope FM.  Linkage of autosomal dominant dystrophic epidermolysis bullosa in three British families to the marker D3S2 close to the COL7A1 . J Med Genet . 1992;;29:381-382.
16 +
Hovnanian A, Duquesnoy P, Blanchet-Bardon C, et al.  Genetic linkage of recessive dystrophic epidermolysis bullosa to the type VII collagen gene . J Clin Invest . 1992;;90:1032-1036.
17 +
Sakai LY, Keene DR, Morris NP, Burgeson RE.  Type VII collagen is a major structural component of anchoring fibrils . J Cell Biol . 1986;;103:1577-1586.
18 +
Burgeson RE, Lunstrum GP, Rokosova B, Rimberg CS, Rosenbaum LM, Keene DR.  The structure and function of type VII collagen . Ann N Y Acad Sci U S A . 1990;;580:32-43.
19 +
Marinkovich MP.  The molecular genetics of basement membrane diseases . Arch Dermatol . 1993;;129:1557-1565.
20 +
Bruckner-Tuderman L.  Collagens of the dermo-epidermal junction: role in bullous disorders . Eur J Dermatol . 1991;;1:89-100.
21 +
McGrath JA, Schofield OMV, Mayou BJ, McKee PH, Eady RAJ.  Epidermolysis bullosa complicated by squamous cell carcinoma: report of 10 cases . J Cutan Pathol . 1992;;19:116-123.
22 +
Gedde-Dahl T.  Clinical heterogeneity in epidermolysis bullosa: speculations on causation and consequence for research . J Invest Dermatol . 1986;;86:91-93.
23 +
Anton-Lamprecht I, Schnyder UW.  Epidermolysis bullosa dystrophica dominans: ein Defect der anchoring Fibrils? Dermatologica . 1973;;147:289-298.
24 +
Tidman MJ, Eady RAJ.  Evaluation of anchoring fibrils and other components of the dermal-epidermal junction in dystrophic epidermolysis bullosa by a quantitative ultrastructural technique . J Invest Dermatol . 1985;;84:374-377.
25 +
Tidman MJ, Eady RAJ.  Ultrastructural morphometry of normal human dermalepidermal junction: the influence of age, sex, and body region on laminar and nonlaminar components . J Invest Dermatol . 1984;;83:448-453.
26 +
Briggaman RA, Wheeler CE.  Epidermolysis bullosa dystrophica recessive: a possible role of anchoring fibrils in the pathogenesis . J Invest Dermatol . 1975;; 65:203-211.
27 +
Bruckner-Tuderman L, Mitsuhashi Y, Schnyder UW, Bruckner P.  Anchoring fibrils and type VII collagen are absent from skin in severe recessive dystrophic epidermolysis bullosa . J Invest Dermatol . 1989;;93:3-9.
28 +
McGrath JA, Ishida-Yamamoto A, O'Grady A, Leigh IM, Eady RAJ.  Structural variations in anchoring fibrils in dystrophic epidermolysis bullosa: correlation with type VII collagen expression . J Invest Dermatol . 1993;;100:366-372.
29 +
Fine JD, Daniels A, Zeng L, Cronce D, Briggaman R.  Comparative analysis of the sensitivity and specificity of altered expression of anchoring fibrils and type VII collagen for diagnosis and subclassification of dystrophic epidermolysis bullosa subsets . J Invest Dermatol . 1993;;100:532. Abstract.
30 +
Hashimoto I, Schnyder UW, Anton-Lamprecht I, Gedde-Dahl T.  Ultrastructural studies in epidermolysis bullosa hereditaria, III: recessive dystrophic types with dermolytic blistering (Hallopeau-Siemens types and inverse type) . Arch Dermatol Res . 1976;;256:137-150
31 +
Bruckner-Tuderman L, Niemi KM, Kero M, Schnyder UW, Reunala T.  Type VII collagen is expressed but anchoring fibrils are defective in dystrophic epidermolysis bullosa inversa . Br J Dermatol . 1990;;122:383-390.
32 +
Bruckner-Tuderman L, Winberg JO, Anton-Lamprecht I, Schnyder UW, GeddeDahl TJ.  Anchoring fibrils, collagen VII, and neutral metalloproteases in recessive dystrophic epidermolysis bullosa inversa . J Invest Dermatol . 1992;;99:550-558.
33 +
Pearson RW.  Studies on the pathogenesis of epidermolysis bullosa . J Invest Dermatol . 1962;;39:551-575.
34 +
Bauer EA.  Collagenase in recessive dystrophic epidermolysis bullosa . Ann N Y Acad Sci . 1986;;460:311-320.
35 +
Bauer EA, Eisen AZ.  Recessive dystrophic epidermolysis bullosa: evidence for increased collagenase as a genetic characteristic in cell culture . J Exp Med . 1978;;148:1378-1387.
36 +
Stricklin PG, Welgus HG, Bauer EA.  Human skin collagenase in recessive dystrophic epidermolysis bullosa: purification of a mutant enzyme from fibroblast cultures . J Clin Invest . 1982;;69:1373-1383.
37 +
Seltzer JL, Eisen AZ, Bauer EA, Morris NP, Glanville RW, Burgeson RE.  Cleavage of type VII collagen by interstitial collagenase and type IV collagenase (gelatinase) derived from human skin . J Biol Chem . 1989;;264:3822-3826.
38 +
Winberg JO, Gedde-Dahl T, Bauer EA.  Collagenase expression in skin fibroblasts from families with recessive dystrophic epidermolysis bullosa . J Invest Dermatol . 1989;;92:82-85.
39 +
Hovnanian A, Duquesnoy P, Amselem S, et al.  Exclusion of linkage between the collagenase gene and generalized recessive dystrophic epidermolysis bullosa phenotype . J Clin Invest . 1991;;88:1716-1721.
40 +
Colombi M, Gardella R, Zoppi N, et al.  Exclusion of stromelysin-1, stromelysin-2, interstitial collagenase and fibronectin genes as the mutant loci in a family with recessive epidermolysis bullosa dystrophica and a form of cerebella ataxia . Hum Genet . 1992;;89:503-507.
41 +
Heagerty AHM, Kennedy AR, Leigh IM, Purkis P, Eady RAJ.  Identification of an epidermal basement membrane defect in recessive forms of dystrophic epidermolysis bullosa by LH7:2 monoclonal antibody: use in diagnosis . Br J Dermatol . 1986;;115:125-131.
42 +
Rusenko KW, Gammon WR, Fine JD, Briggamann RA.  The carboxy-terminal domain of type VII collagen is present at the basement membrane in recessive dystrophic epidermolysis bullosa . J Invest Dermatol . 1989;;92:623-627.
43 +
Bruckner-Tuderman L, Rüegger S, Odermatt B, Mitsuhashi Y, Schnyder UW.  Lack of type VII collagen in unaffected skin of patients with severe recessive dystrophic epidermolysis bullosa . Dermatologica . 1988;;176:57-64.
44 +
Heagerty AHM, Kennedy AR, Gunner DB, Eady RAJ.  Rapid prenatal diagnosis and exclusion of epidermolysis bullosa using novel antibody probes . J Invest Dermatol . 1986;;86:603-605.
45 +
Leigh IM, Eady RAJ, Heagerty AHM, Purkis PE, Whitehead PA, Burgeson RE.  Type VII collagen is a normal component of epidermal basement membrane, which shows altered expression in recessive dystrophic epidermolysis bullosa . J Invest Dermatol . 1988;;90:639-642.
46 +
König A, Lauharanta J, Bruckner-Tuderman L.  Keratinocytes and fibroblasts from a patient with mutilating dystrophic epidermolysis bullosa synthesize drastically reduced amounts of collagen VII: lack of effect of transforming growth factor β . J Invest Dermatol . 1992;;99:808-812.
47 +
Fine JD, Horiguchi Y, Stein DH, Esterly NB, Leigh IM.  Intraepidermal type VII collagen: evidence for abnormal intracytoplasmic processing of a major basement membrane protein in rare patients with dominant and possibly localized recessive forms of dystrophic epidermolysis bullosa . J Am Acad Dermatol . 1990;;22:188-195.
48 +
Smith LT, Sybert VP.  Intra-epidermal retention of type VII collagen in a patient with recessive dystrophic epidermolysis bullosa . J Invest Dermatol . 1990;;94: 261-264.
49 +
Parente MG, Chung LC, Ryynänen J, et al.  Human type VII collagen: cDNA cloning and chromosomal mapping of the gene . Proc Natl Acad Sci U S A . 1991;;88:6931-6935.
50 +
Christiano AM, Greenspan DS, Hoffman GG, et al.  A missense mutation in type VII collagen in two affected siblings with recessive dystrophic epidermolysis bullosa . Nature Genet . 1993;;4:62-66.
51 +
Hilal L, Rochat A, Duquesnoy P, et al. A homozygous insertion-deletion in COL7A1 predicting a truncated protein in the Hallopeau-Siemens type of recessive dystrophic epidermolysis bullosa. Nature Genet. In press.
52 +
Hilal L, Hovnanian A, Duquesnoy P, et al.  Characterization of mutations within the COL7A1 gene in patients with recessive dystrophic epidermolysis bullosa . J Invest Dermatol . 1993;;100:499. Abstract.
53 +
Willing MC, Pruchno CJ, Atkinson M, Byers PH.  Osteogenesis imperfecta type I is commonly due to a COL1A1 null allele of type I collagen . Am J Hum Genet . 1992;;51:508-515.
54 +
Prockop DJ.  Mutations in collagen genes as a cause of connective-tissue diseases . N Engl J Med . 1992;;326:540-546.
55 +
Prockop DJ, Baldwin CT, Constantinou CD.  Mutations in type I procollagen genes that cause osteogenesis imperfecta . Adv Hum Genet . 1990;;19:105-132.
56 +
Pihlajaniemi T, Dickson LA, Pope FM, et al.  Osteogenesis imperfecta: cloning of a pro-α2(1) collagen gene with a frameshift mutation . J Biol Chem . 1984;; 259:12941-12944.
57 +
Tromp G, Prockop D.  Single base mutation in the proα2(1) collagen gene that causes efficient splicing of RNA from exon 27 to exon 29 and synthesis of a shortened but in-frame proαa2(1) chain . Proc Natl Acad Sci U S A . 1988;;85: 5254-5258.
58 +
Bonadio J, Ramirez F, Barr M.  An intron mutation in the human α1(1) collagen gene alters the efficiency of pre-mRNA splicing and is associated with osteogenesis imperfecta type II . J Biol Chem 1990;;265:2262-2268.
59 +
Hovnanian A, Hilal L, Blanchet-Bardon C, et al.  Prenatal diagnosis of recessive dystrophic epidermolysis bullosa by Pvull intragenic type VII collagen gene polymorphism . J Invest Dermatol . 1993;;100:515. Abstract.
60 +
Christiano AM, Uitto J.  DNA-based prenatal diagnosis of heritable skin diseases . Arch Dermatol . 1993;;129:1455-1459.

Figures

Tables

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Gedde-Dahl TJ, Anton-Lamprecht I.  Epidermolysis bullosa . In: Rimoin DL, ed. Principles and Practice of Medical Genetics . New York, NY: Churchill Livingstone; 1990;:855-876.
2 +
Fine JD, Bauer EA, Briggaman RA, et al.  Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa: a consensus report by the Subcommittee on Diagnosis and Classification of the National Epidermolysis Bullosa Registry . J Am Acad Dermatol . 1991;;24:119-135.
3 +
Lin AN, Carter DM. Epidermolysis Bullosa: Basic and Clinical Aspects . New York, NY: Springer-Verlag NY Inc; 1992;.
4 +
Epstein EH Jr.  Molecular genetics of epidermolysis bullosa . Science . 1992;; 256:799-803.
5 +
Fuchs E.  Genetic skin disorders of keratin . J Invest Dermatol . 1992;;99:671674.
6 +
Bonifas JM, Rothman AL, Epstein EH Jr.  Epidermolysis bullosa simplex: evidence in two families for keratin gene abnormalities . Science . 1991;;254:1202-1205.
7 +
Coulombe PA, Hutton ME, Letai A, Hebert A, Paller AS, Fuchs E.  Point mutations in human keratin 14 genes of epidermolysis bullosa simplex patients: genetic and functional analyses . Cell . 1991;;66:1301-1311.
8 +
Lane EB, Rugg EL, Navsaria H, et al.  A mutation in the conserved helix termination peptide of keratin 5 in hereditary skin blistering . Nature . 1992;;356:244-246.
9 +
Dong W, Ryynänen M, Uitto J.  Identification of a leucine-to-proline mutation in the keratin 5 gene in a family with the generalized Köbner type of epidermolysis bullosa simplex . Hum Mut . 1993;;2:94-102.
10 +
Hovnanian A, Pollack E, Hilal L, et al.  A missense mutation in the rod domain of keratin 14 associated with recessive epidermolysis bullosa simplex . Nature Genet . 1993;;3:327-332.
11 +
Meneguzzi G, Marinkovich MP, Aberdam D, Pisani A, Burgeson R, Ortonne JP.  Kalinin is abnormally expressed in epithelial basement membranes of Herlitz's junctional epidermolysis bullosa patients . Exp Dermatol . 1993;;1:221-229.
12 +
Ryynänen M, Knowlton RG, Parente MG, Chung LC, Chu ML, Uitto J.  Human type VII collagen: genetic linkage of the gene (COL7A1) on chromosome 3 to dominant dystrophic epidermolysis bullosa . Am J Hum Genet . 1991;;49:797-803.
13 +
Ryynänen M, Ryynänen J, Sollberg S, lozzo RV, Knowlton RG, Uitto J.  Genetic linkage of type VII collagen (COL7A1) to dominant dystrophic epidermolysis bullosa in families with abnormal anchoring fibrils . J Clin Invest . 1992;;89:974-980.
14 +
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.
15 +
Al-Imara L, Richards AJ, Eady RAJ, Leigh IM, Farrall M, Pope FM.  Linkage of autosomal dominant dystrophic epidermolysis bullosa in three British families to the marker D3S2 close to the COL7A1 . J Med Genet . 1992;;29:381-382.
16 +
Hovnanian A, Duquesnoy P, Blanchet-Bardon C, et al.  Genetic linkage of recessive dystrophic epidermolysis bullosa to the type VII collagen gene . J Clin Invest . 1992;;90:1032-1036.
17 +
Sakai LY, Keene DR, Morris NP, Burgeson RE.  Type VII collagen is a major structural component of anchoring fibrils . J Cell Biol . 1986;;103:1577-1586.
18 +
Burgeson RE, Lunstrum GP, Rokosova B, Rimberg CS, Rosenbaum LM, Keene DR.  The structure and function of type VII collagen . Ann N Y Acad Sci U S A . 1990;;580:32-43.
19 +
Marinkovich MP.  The molecular genetics of basement membrane diseases . Arch Dermatol . 1993;;129:1557-1565.
20 +
Bruckner-Tuderman L.  Collagens of the dermo-epidermal junction: role in bullous disorders . Eur J Dermatol . 1991;;1:89-100.
21 +
McGrath JA, Schofield OMV, Mayou BJ, McKee PH, Eady RAJ.  Epidermolysis bullosa complicated by squamous cell carcinoma: report of 10 cases . J Cutan Pathol . 1992;;19:116-123.
22 +
Gedde-Dahl T.  Clinical heterogeneity in epidermolysis bullosa: speculations on causation and consequence for research . J Invest Dermatol . 1986;;86:91-93.
23 +
Anton-Lamprecht I, Schnyder UW.  Epidermolysis bullosa dystrophica dominans: ein Defect der anchoring Fibrils? Dermatologica . 1973;;147:289-298.
24 +
Tidman MJ, Eady RAJ.  Evaluation of anchoring fibrils and other components of the dermal-epidermal junction in dystrophic epidermolysis bullosa by a quantitative ultrastructural technique . J Invest Dermatol . 1985;;84:374-377.
25 +
Tidman MJ, Eady RAJ.  Ultrastructural morphometry of normal human dermalepidermal junction: the influence of age, sex, and body region on laminar and nonlaminar components . J Invest Dermatol . 1984;;83:448-453.
26 +
Briggaman RA, Wheeler CE.  Epidermolysis bullosa dystrophica recessive: a possible role of anchoring fibrils in the pathogenesis . J Invest Dermatol . 1975;; 65:203-211.
27 +
Bruckner-Tuderman L, Mitsuhashi Y, Schnyder UW, Bruckner P.  Anchoring fibrils and type VII collagen are absent from skin in severe recessive dystrophic epidermolysis bullosa . J Invest Dermatol . 1989;;93:3-9.
28 +
McGrath JA, Ishida-Yamamoto A, O'Grady A, Leigh IM, Eady RAJ.  Structural variations in anchoring fibrils in dystrophic epidermolysis bullosa: correlation with type VII collagen expression . J Invest Dermatol . 1993;;100:366-372.
29 +
Fine JD, Daniels A, Zeng L, Cronce D, Briggaman R.  Comparative analysis of the sensitivity and specificity of altered expression of anchoring fibrils and type VII collagen for diagnosis and subclassification of dystrophic epidermolysis bullosa subsets . J Invest Dermatol . 1993;;100:532. Abstract.
30 +
Hashimoto I, Schnyder UW, Anton-Lamprecht I, Gedde-Dahl T.  Ultrastructural studies in epidermolysis bullosa hereditaria, III: recessive dystrophic types with dermolytic blistering (Hallopeau-Siemens types and inverse type) . Arch Dermatol Res . 1976;;256:137-150
31 +
Bruckner-Tuderman L, Niemi KM, Kero M, Schnyder UW, Reunala T.  Type VII collagen is expressed but anchoring fibrils are defective in dystrophic epidermolysis bullosa inversa . Br J Dermatol . 1990;;122:383-390.
32 +
Bruckner-Tuderman L, Winberg JO, Anton-Lamprecht I, Schnyder UW, GeddeDahl TJ.  Anchoring fibrils, collagen VII, and neutral metalloproteases in recessive dystrophic epidermolysis bullosa inversa . J Invest Dermatol . 1992;;99:550-558.
33 +
Pearson RW.  Studies on the pathogenesis of epidermolysis bullosa . J Invest Dermatol . 1962;;39:551-575.
34 +
Bauer EA.  Collagenase in recessive dystrophic epidermolysis bullosa . Ann N Y Acad Sci . 1986;;460:311-320.
35 +
Bauer EA, Eisen AZ.  Recessive dystrophic epidermolysis bullosa: evidence for increased collagenase as a genetic characteristic in cell culture . J Exp Med . 1978;;148:1378-1387.
36 +
Stricklin PG, Welgus HG, Bauer EA.  Human skin collagenase in recessive dystrophic epidermolysis bullosa: purification of a mutant enzyme from fibroblast cultures . J Clin Invest . 1982;;69:1373-1383.
37 +
Seltzer JL, Eisen AZ, Bauer EA, Morris NP, Glanville RW, Burgeson RE.  Cleavage of type VII collagen by interstitial collagenase and type IV collagenase (gelatinase) derived from human skin . J Biol Chem . 1989;;264:3822-3826.
38 +
Winberg JO, Gedde-Dahl T, Bauer EA.  Collagenase expression in skin fibroblasts from families with recessive dystrophic epidermolysis bullosa . J Invest Dermatol . 1989;;92:82-85.
39 +
Hovnanian A, Duquesnoy P, Amselem S, et al.  Exclusion of linkage between the collagenase gene and generalized recessive dystrophic epidermolysis bullosa phenotype . J Clin Invest . 1991;;88:1716-1721.
40 +
Colombi M, Gardella R, Zoppi N, et al.  Exclusion of stromelysin-1, stromelysin-2, interstitial collagenase and fibronectin genes as the mutant loci in a family with recessive epidermolysis bullosa dystrophica and a form of cerebella ataxia . Hum Genet . 1992;;89:503-507.
41 +
Heagerty AHM, Kennedy AR, Leigh IM, Purkis P, Eady RAJ.  Identification of an epidermal basement membrane defect in recessive forms of dystrophic epidermolysis bullosa by LH7:2 monoclonal antibody: use in diagnosis . Br J Dermatol . 1986;;115:125-131.
42 +
Rusenko KW, Gammon WR, Fine JD, Briggamann RA.  The carboxy-terminal domain of type VII collagen is present at the basement membrane in recessive dystrophic epidermolysis bullosa . J Invest Dermatol . 1989;;92:623-627.
43 +
Bruckner-Tuderman L, Rüegger S, Odermatt B, Mitsuhashi Y, Schnyder UW.  Lack of type VII collagen in unaffected skin of patients with severe recessive dystrophic epidermolysis bullosa . Dermatologica . 1988;;176:57-64.
44 +
Heagerty AHM, Kennedy AR, Gunner DB, Eady RAJ.  Rapid prenatal diagnosis and exclusion of epidermolysis bullosa using novel antibody probes . J Invest Dermatol . 1986;;86:603-605.
45 +
Leigh IM, Eady RAJ, Heagerty AHM, Purkis PE, Whitehead PA, Burgeson RE.  Type VII collagen is a normal component of epidermal basement membrane, which shows altered expression in recessive dystrophic epidermolysis bullosa . J Invest Dermatol . 1988;;90:639-642.
46 +
König A, Lauharanta J, Bruckner-Tuderman L.  Keratinocytes and fibroblasts from a patient with mutilating dystrophic epidermolysis bullosa synthesize drastically reduced amounts of collagen VII: lack of effect of transforming growth factor β . J Invest Dermatol . 1992;;99:808-812.
47 +
Fine JD, Horiguchi Y, Stein DH, Esterly NB, Leigh IM.  Intraepidermal type VII collagen: evidence for abnormal intracytoplasmic processing of a major basement membrane protein in rare patients with dominant and possibly localized recessive forms of dystrophic epidermolysis bullosa . J Am Acad Dermatol . 1990;;22:188-195.
48 +
Smith LT, Sybert VP.  Intra-epidermal retention of type VII collagen in a patient with recessive dystrophic epidermolysis bullosa . J Invest Dermatol . 1990;;94: 261-264.
49 +
Parente MG, Chung LC, Ryynänen J, et al.  Human type VII collagen: cDNA cloning and chromosomal mapping of the gene . Proc Natl Acad Sci U S A . 1991;;88:6931-6935.
50 +
Christiano AM, Greenspan DS, Hoffman GG, et al.  A missense mutation in type VII collagen in two affected siblings with recessive dystrophic epidermolysis bullosa . Nature Genet . 1993;;4:62-66.
51 +
Hilal L, Rochat A, Duquesnoy P, et al. A homozygous insertion-deletion in COL7A1 predicting a truncated protein in the Hallopeau-Siemens type of recessive dystrophic epidermolysis bullosa. Nature Genet. In press.
52 +
Hilal L, Hovnanian A, Duquesnoy P, et al.  Characterization of mutations within the COL7A1 gene in patients with recessive dystrophic epidermolysis bullosa . J Invest Dermatol . 1993;;100:499. Abstract.
53 +
Willing MC, Pruchno CJ, Atkinson M, Byers PH.  Osteogenesis imperfecta type I is commonly due to a COL1A1 null allele of type I collagen . Am J Hum Genet . 1992;;51:508-515.
54 +
Prockop DJ.  Mutations in collagen genes as a cause of connective-tissue diseases . N Engl J Med . 1992;;326:540-546.
55 +
Prockop DJ, Baldwin CT, Constantinou CD.  Mutations in type I procollagen genes that cause osteogenesis imperfecta . Adv Hum Genet . 1990;;19:105-132.
56 +
Pihlajaniemi T, Dickson LA, Pope FM, et al.  Osteogenesis imperfecta: cloning of a pro-α2(1) collagen gene with a frameshift mutation . J Biol Chem . 1984;; 259:12941-12944.
57 +
Tromp G, Prockop D.  Single base mutation in the proα2(1) collagen gene that causes efficient splicing of RNA from exon 27 to exon 29 and synthesis of a shortened but in-frame proαa2(1) chain . Proc Natl Acad Sci U S A . 1988;;85: 5254-5258.
58 +
Bonadio J, Ramirez F, Barr M.  An intron mutation in the human α1(1) collagen gene alters the efficiency of pre-mRNA splicing and is associated with osteogenesis imperfecta type II . J Biol Chem 1990;;265:2262-2268.
59 +
Hovnanian A, Hilal L, Blanchet-Bardon C, et al.  Prenatal diagnosis of recessive dystrophic epidermolysis bullosa by Pvull intragenic type VII collagen gene polymorphism . J Invest Dermatol . 1993;;100:515. Abstract.
60 +
Christiano AM, Uitto J.  DNA-based prenatal diagnosis of heritable skin diseases . Arch Dermatol . 1993;;129:1455-1459.

Correspondence

Submit a Letter
CME Course for:


You need to register in order to view this quiz.


To understand the clinical management of acute heart failure syndromes.
Accreditation Information The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
To view and print your certificate and access a summary of your CME courses go to My CME.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
Compression-Only CPR: Pushing the Science Forward
Cone
AAM 2010;304:1493-1495.
All you need to read in the other general journals
BMJ 2010;341:c5893-c1494.
Submit a Comment

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

© 2012 American Medical Association. All Rights Reserved.
Powered bySilverchair Information Systems