CED
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Kallin syndrome associated with vitiligo M. A. El Darouti, M. S. El Hawary and R. M. Abdel Hay Department of Dermatology, Faculty of Medicine, Cairo University, Cairo, Egypt doi:10.1111/ced.12463
Summary
Kallin syndrome (KS) is a variant of epidermolysis bullosa simplex (EBS), which, in addition to the classic features of EBS, also presents with deafness, alopecia, hypodontia and nail dystrophy. We report the case of a 17-year-old boy who presented to our clinic with trauma-induced skin blistering, alopecia, deafness, dental caries, nail dystrophy and vitiliginous areas. The skin blisters had been appearing since birth, and healed without scarring. The vitiliginous areas were unrelated to the sites of the blisters. Electron microscopy of the skin blisters was diagnostic of EBS, and the depigmented lesions were similar to those of vitiligo. An association of vitiligo with EBS has not been reported previously. Multiple genetic findings have confirmed a role for keratin in regulating skin pigmentation. Apoptosis of melanosome-bearing keratinocytes may participate in the reduction of melanin density and result in depigmentation. Further studies on the defective proteins in KS may clarify the mechanism underlying the association with vitiligo.
Kallin syndrome (KS) is an extremely rare variant of epidermolysis bullosa simplex (EBS) that shows (in addition to the typical trauma-induced blisters) the features of deafness, alopecia, hypodontia and nail dystrophy. The syndrome was first described by Gamborg Nielsen,1 who named it ‘syndroma Kallin’ after the surname of the two patients reported in that study, who were the first patients with this syndrome; however, the report did not describe deafness in either of these two patients. Two genetic possibilities were suggested: an autosomal recessive genetic trait or a gonadal mosaicism with an early dominant gene mutation. We report the case of an adolescent boy with KS, who had areas of depigmentation similar to vitiligo. To our knowledge, the association of vitiligo and KS has not been reported previously.
Report The proband was a 17-year-old boy, who was born after a normal pregnancy to consanguineous parents. Correspondence: Dr Rania M. Abdel Hay, 13th Abrag Othman, Kournish el Maadi, Cairo 11431, Egypt E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 4 February 2014
ª 2014 British Association of Dermatologists
He was the fourth child of his parents; the previous children were three normal girls. The important clinical features in our patient included skin blisters, alopecia, deafness, dental caries, hypodontia, nail dystrophy and vitiligo (Fig. 1). The blisters had been occurring since birth; they developed most often in relation to trauma, and healed without scarring, leaving hyperpigmented areas. The patient also had vitiliginous areas, which were unrelated to the blister sites. The blistering favoured a diagnosis of EBS. Histological examination of a skin biopsy taken from a fresh blister showed subepidermal clefting with no inflammatory infiltrate. Electron microscopy showed a subepidermal blister (Fig. 2). The basal keratinocytes exhibited vacuolar degeneration and desmosomal detachment; some of these cells showed nuclear degeneration, and complete disruption (cytolysis) was observed in some areas (Fig. 2). The electron microscopiy picture was diagnostic of EBS. The depigmented lesions showed absence of melanocytes from the base of the epidermis, and loss of keratinocyte pigment, diagnostic of vitiligo. Based on the clinical, histopathological and electron microscopy results, our provisional diagnosis was EBS. However, the presence of the nail dystrophy, alopecia,
Clinical and Experimental Dermatology (2015) 40, pp35–38
35
Kallin syndrome associated with vitiligo M. A. El Darouti et al.
(a)
(b)
(d)
(c)
(e)
(f)
Figure 1 A male patient presenting with skin blisters that healed with hyperpigmentation, along with alopecia and vitiligenous areas.
(a–f) Photos of the patient showing (a) dental caries, (b) alopecia, (c,d) nail dystrophy, and (c–f) fresh blisters on (c) hands (d) feet, (e) upper and (f) lower limbs.
deafness and hypodontia raised questions about the exact type of EBS. The only type of EBS showing these symptoms in addition to the classic features of EBS is KS.1 Therefore, we diagnosed the patient as having KS associated with vitiligo. It is noteworthy that KS, probably because of its extreme rarity, was not included in the most recent classification of EBS (Table 1).2 The association of vitiligo with EBS had not been reported previously, to our knowledge. Skin pigmentation is the result of an intimate partnership between keratinocytes and melanocytes. Multiple genetic findings have identified a role for keratin in regulating skin pigmentation. Distinct mutations in keratin (K)5 or K1 may be linked to the occurrence of the small hyperpigmented or hypopigmented spots seen in EBS with mottled pigmentation.3 Mutations in K5 can result in EBS–migratory circinate erythema, which is also associated with hyperpigmented or hypopigmented skin patches.4 Dowling–Degos disease (a variant of ectodermal dysplasia that shows reticulate hyperpigmentation of the flexures) has been linked to
36
Clinical and Experimental Dermatology (2015) 40, pp35–38
K5 mutations,5 while other variants of ectodermal dysplasia, such as dermatopathia pigmentosa reticularis (which shows reticulate hyperpigmentation, nonscarring alopecia and onychodystrophy) and Naegeli– Franceschetti–Jadassohn syndrome (which shows, in addition to the blisters, the features of reticulate hyperpigmentation, hypohidrosis and dental anomalies) have been linked to K14 mutations.6 Lack of a functional d subunit of the adaptor-like protein complex adaptor protein (AP)3, which normally binds various intermediate filament proteins, including K5 and K14, has been reported from studies using the mocha mouse, which has a diluted coat and eye colour phenotype.7 Accordingly, it may be assumed that genes that may be defective or mutated in KS (possible examples might be K5 or K14), may be related to the development of depigmented patches seen in our patient. Mutant keratin may increase the susceptibility of keratinocytes to tumour necrosis factor (TNF)-ainduced apoptosis,8 before the occurrence of traumainduced basal cell lysis. Apoptosis of melanosomebearing keratinocytes may eventually participate in
ª 2014 British Association of Dermatologists
Kallin syndrome associated with vitiligo M. A. El Darouti et al.
(b)
(a)
(c)
(d)
Figure 2 Electron microscopy showing (a) sub-epidermal blister, (b) Adjacent normal skin with intact desmosomes, absence of vacuolar
or nuclear degeneration, (c) Vacuolar degeneration of the basal keratinocytes, desmosomal detachment and nuclear degeneration, (d) Complete disruption (cytolysis) of basal keratinocytes.
Table 1 Subtypes of epidermolysis bullosa simplex (EBS)2. Type
Defective protein
Clinical picture
Basal Dowling–Meara EBS EBS with mottled pigmentation Generalized (Koebner) EBS EBS with muscle dystrophy
Keratin (K)5, K14 K5, K14 K5 K5, K14 Plectin
EBS with pyloric atresia EBS ogna EBS–migratory circinate erythema EBS Mendes De Costa Kallin syndrome Suprabasal Lethal acantholytic EB
Plectin, integrin a6b4 Plectin K5 Unknown Unknown
Primary involvement of the palms and soles with or without hyperhydrosis Affects mainly the oral mucosa in the form of grouped herpetiform blisters Blisters and reticulate hyperpigmented macules Generalized blisters and palmoplantar hyperkeratosis and erosions Variable blistering activity, muscular dystrophy later in life with or without dental anomalies Severe generalized blisters and pyloric atresia at birth. Usually fatal during infancy – Migratory circinate erythema with vesiculation at the advancing edge
Ectodermal dysplasia–skin fragility syndrome EBS superficialis
Desmoplakin Plakophillin 1 Unknown
Blisters, deafness, alopecia, hypodontia and nail dystrophy Rapidly generalized progressive epidermolysis, universal alopecia, shedding of nails and natal teeth Widespread skin fragility, alopecia, nail dystrophy and focal keratoderma with painful fissures Superficial peeling of the skin with no obvious blisters
the reduction in melanin density, and result in depigmentation. Further studies on the defective proteins in KS and possible related gene mutations may clarify the mechanism underlying the association of vitiligo. Another unusual feature observed in our patient was the presence of hypodontia and marked dental caries. It was found previously that cytokeratin 5 binds to the amelogenin trityrosyl motif peptide
ª 2014 British Association of Dermatologists
(ATMP) sequence of amelogenin, and is suspected to play a chaperone role for nascent amelogenin polypeptides.9 Thus, keratin mutations are likely to contribute to the enamel defects present in KS. The congenital alopecia in our patient may be related to a possible link between K5 or K14 mutations and hair loss. Tong and Coulombe10 identified K17 and TNF-a as two novel and interdependent
Clinical and Experimental Dermatology (2015) 40, pp35–38
37
Kallin syndrome associated with vitiligo M. A. El Darouti et al.
regulators of hair cycling. They also revealed that K17-null skin keratinocytes in primary culture are selectively more sensitive to TNF-a, and that this occurs via an interaction between K17 and the TNF receptor 1 (TNFR1)-associated death domain protein (TRADD).10 The association of K14 with TNF-a induced apoptosis is still controversial; it is unclear whether this protects from apoptosis via sequestration of TRADD away from TNFR1 (as does K18), or increases apoptosis (as does K17).11 These questions need to be explored further, but the current data point to a possible intimate relationship between K14 (and possibly K17 mutations) and the alopecia observed in KS. Genetic mapping is of prime importance to solve this puzzle and to determine if the mutated keratins in this unique type of EBS are restricted to K5 and K14 only, or if there is an additional mutation of K17, resulting in the multiple associations present in our patient. Unfortunately, genetic study of our patient was not possible.
Learning points KS is an extremely rare variant of EBS. The features associated with KS include
trauma-induced blisters, deafness, alopecia, hypodontia and nail dystrophy. The blisters in EBS occur from birth, developing after trauma and healing without scarring. Skin pigmentation is the result of an intimate partnership between keratinocytes and melanocytes. Multiple genetic findings have formalized a role for keratin in regulating skin pigmentation. Two genetic possibilities for KS have been suggested: an autosomal recessive genetic trait or a gonadal mosaicism with an early dominant gene mutation.
2
3
4
5
6
7
8
9
10
11
nail disorders: a new syndrome. Acta Derm Venereol 1985; 65: 526–30. Fine JD, Eady RA, Bauer EA et al. The classification of inherited epidermolysis bullosa (EB); report of the third International Consensus Meeting on diagnosis and classification of EB. J Am Acad Dermatol 2008; 58: 931– 50. Uttam J, Hutton E, Coulombe PA et al. The genetic basis of epidermolysis bullosa simplex with mottled pigmentation. Proc Natl Acad Sci USA 1996; 93: 9079– 84. Gu LH, Kim SC, Ichiki Y et al. A usual frameshift and delayed termination codon mutation in keratin 5 causes a novel type of epidermolysis bullosa simplex with migratory circinate erythema. J Invest Dermatol 2003; 121: 482–5. Betz RC, Betz RC, Planko L et al. Loss-of-function mutations in the keratin 5 gene lead to Dowling-Degos disease. Am J Hum Genet 2006; 78: 510–19. Lugassy J, Itin P, Ishida-Yamamoto A et al. Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: two allelic ectodermal dysplasias caused by dominant mutations in KRT14. Am J Hum Genet 2006; 79: 724–30. Styers ML, Kowalczyk AP, Faundez V. Intermediate filaments and vesicular membrane traffic: the odd couple’s first dance? Traffic 2005; 6: 359–65. Lugassy J, McGrath JA, Itin P et al. KRT14 haploinsufficiency results in increased susceptibility of keratinocytes to TNF-alpha-induced apoptosis and causes Naegeli-Franceschetti-Jadassohn syndrome. J Invest Dermatol 2008; 128: 1517–24. Ravindranath RM, Basilrose RM Sr, Ravindranath NH, Vaitheesvaran B. Amelogenin interacts with cytokeratin-5 in ameloblasts during enamel growth. J Biol Chem 2003; 278: 20293–302. Tong X, Coulombe PA. Keratin 17 modulates hair follicle cycling in a TNF-a dependent fashion. Genes Dev 2006; 20: 1353–64. Yoneda K, Furukawa T, Zheng YJ et al. An autocrine/ paracrine loop linking keratin 14 aggregates to tumor necrosis factor a-mediated cytotoxicity in a keratinocyte model of epidermolysis bullosa simplex. J Biol Chem 2004; 279: 7296–303.
References 1 Gamborg Nielsen P, Sj€ olund E. Epidermolysis bullosa simplex localisata associated with anodontia, hair and
38
Clinical and Experimental Dermatology (2015) 40, pp35–38
ª 2014 British Association of Dermatologists
This document is a scanned copy of a printed document. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material.
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Kallin syndrome associated with vitiligo M. A. El Darouti, M. S. El Hawary and R. M. Abdel Hay Department of Dermatology, Faculty of Medicine, Cairo University, Cairo, Egypt doi:10.1111/ced.12463
Summary
Kallin syndrome (KS) is a variant of epidermolysis bullosa simplex (EBS), which, in addition to the classic features of EBS, also presents with deafness, alopecia, hypodontia and nail dystrophy. We report the case of a 17-year-old boy who presented to our clinic with trauma-induced skin blistering, alopecia, deafness, dental caries, nail dystrophy and vitiliginous areas. The skin blisters had been appearing since birth, and healed without scarring. The vitiliginous areas were unrelated to the sites of the blisters. Electron microscopy of the skin blisters was diagnostic of EBS, and the depigmented lesions were similar to those of vitiligo. An association of vitiligo with EBS has not been reported previously. Multiple genetic findings have confirmed a role for keratin in regulating skin pigmentation. Apoptosis of melanosome-bearing keratinocytes may participate in the reduction of melanin density and result in depigmentation. Further studies on the defective proteins in KS may clarify the mechanism underlying the association with vitiligo.
Kallin syndrome (KS) is an extremely rare variant of epidermolysis bullosa simplex (EBS) that shows (in addition to the typical trauma-induced blisters) the features of deafness, alopecia, hypodontia and nail dystrophy. The syndrome was first described by Gamborg Nielsen,1 who named it ‘syndroma Kallin’ after the surname of the two patients reported in that study, who were the first patients with this syndrome; however, the report did not describe deafness in either of these two patients. Two genetic possibilities were suggested: an autosomal recessive genetic trait or a gonadal mosaicism with an early dominant gene mutation. We report the case of an adolescent boy with KS, who had areas of depigmentation similar to vitiligo. To our knowledge, the association of vitiligo and KS has not been reported previously.
Report The proband was a 17-year-old boy, who was born after a normal pregnancy to consanguineous parents. Correspondence: Dr Rania M. Abdel Hay, 13th Abrag Othman, Kournish el Maadi, Cairo 11431, Egypt E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 4 February 2014
ª 2014 British Association of Dermatologists
He was the fourth child of his parents; the previous children were three normal girls. The important clinical features in our patient included skin blisters, alopecia, deafness, dental caries, hypodontia, nail dystrophy and vitiligo (Fig. 1). The blisters had been occurring since birth; they developed most often in relation to trauma, and healed without scarring, leaving hyperpigmented areas. The patient also had vitiliginous areas, which were unrelated to the blister sites. The blistering favoured a diagnosis of EBS. Histological examination of a skin biopsy taken from a fresh blister showed subepidermal clefting with no inflammatory infiltrate. Electron microscopy showed a subepidermal blister (Fig. 2). The basal keratinocytes exhibited vacuolar degeneration and desmosomal detachment; some of these cells showed nuclear degeneration, and complete disruption (cytolysis) was observed in some areas (Fig. 2). The electron microscopiy picture was diagnostic of EBS. The depigmented lesions showed absence of melanocytes from the base of the epidermis, and loss of keratinocyte pigment, diagnostic of vitiligo. Based on the clinical, histopathological and electron microscopy results, our provisional diagnosis was EBS. However, the presence of the nail dystrophy, alopecia,
Clinical and Experimental Dermatology (2015) 40, pp35–38
35
Kallin syndrome associated with vitiligo M. A. El Darouti et al.
(a)
(b)
(d)
(c)
(e)
(f)
Figure 1 A male patient presenting with skin blisters that healed with hyperpigmentation, along with alopecia and vitiligenous areas.
(a–f) Photos of the patient showing (a) dental caries, (b) alopecia, (c,d) nail dystrophy, and (c–f) fresh blisters on (c) hands (d) feet, (e) upper and (f) lower limbs.
deafness and hypodontia raised questions about the exact type of EBS. The only type of EBS showing these symptoms in addition to the classic features of EBS is KS.1 Therefore, we diagnosed the patient as having KS associated with vitiligo. It is noteworthy that KS, probably because of its extreme rarity, was not included in the most recent classification of EBS (Table 1).2 The association of vitiligo with EBS had not been reported previously, to our knowledge. Skin pigmentation is the result of an intimate partnership between keratinocytes and melanocytes. Multiple genetic findings have identified a role for keratin in regulating skin pigmentation. Distinct mutations in keratin (K)5 or K1 may be linked to the occurrence of the small hyperpigmented or hypopigmented spots seen in EBS with mottled pigmentation.3 Mutations in K5 can result in EBS–migratory circinate erythema, which is also associated with hyperpigmented or hypopigmented skin patches.4 Dowling–Degos disease (a variant of ectodermal dysplasia that shows reticulate hyperpigmentation of the flexures) has been linked to
36
Clinical and Experimental Dermatology (2015) 40, pp35–38
K5 mutations,5 while other variants of ectodermal dysplasia, such as dermatopathia pigmentosa reticularis (which shows reticulate hyperpigmentation, nonscarring alopecia and onychodystrophy) and Naegeli– Franceschetti–Jadassohn syndrome (which shows, in addition to the blisters, the features of reticulate hyperpigmentation, hypohidrosis and dental anomalies) have been linked to K14 mutations.6 Lack of a functional d subunit of the adaptor-like protein complex adaptor protein (AP)3, which normally binds various intermediate filament proteins, including K5 and K14, has been reported from studies using the mocha mouse, which has a diluted coat and eye colour phenotype.7 Accordingly, it may be assumed that genes that may be defective or mutated in KS (possible examples might be K5 or K14), may be related to the development of depigmented patches seen in our patient. Mutant keratin may increase the susceptibility of keratinocytes to tumour necrosis factor (TNF)-ainduced apoptosis,8 before the occurrence of traumainduced basal cell lysis. Apoptosis of melanosomebearing keratinocytes may eventually participate in
ª 2014 British Association of Dermatologists
Kallin syndrome associated with vitiligo M. A. El Darouti et al.
(b)
(a)
(c)
(d)
Figure 2 Electron microscopy showing (a) sub-epidermal blister, (b) Adjacent normal skin with intact desmosomes, absence of vacuolar
or nuclear degeneration, (c) Vacuolar degeneration of the basal keratinocytes, desmosomal detachment and nuclear degeneration, (d) Complete disruption (cytolysis) of basal keratinocytes.
Table 1 Subtypes of epidermolysis bullosa simplex (EBS)2. Type
Defective protein
Clinical picture
Basal Dowling–Meara EBS EBS with mottled pigmentation Generalized (Koebner) EBS EBS with muscle dystrophy
Keratin (K)5, K14 K5, K14 K5 K5, K14 Plectin
EBS with pyloric atresia EBS ogna EBS–migratory circinate erythema EBS Mendes De Costa Kallin syndrome Suprabasal Lethal acantholytic EB
Plectin, integrin a6b4 Plectin K5 Unknown Unknown
Primary involvement of the palms and soles with or without hyperhydrosis Affects mainly the oral mucosa in the form of grouped herpetiform blisters Blisters and reticulate hyperpigmented macules Generalized blisters and palmoplantar hyperkeratosis and erosions Variable blistering activity, muscular dystrophy later in life with or without dental anomalies Severe generalized blisters and pyloric atresia at birth. Usually fatal during infancy – Migratory circinate erythema with vesiculation at the advancing edge
Ectodermal dysplasia–skin fragility syndrome EBS superficialis
Desmoplakin Plakophillin 1 Unknown
Blisters, deafness, alopecia, hypodontia and nail dystrophy Rapidly generalized progressive epidermolysis, universal alopecia, shedding of nails and natal teeth Widespread skin fragility, alopecia, nail dystrophy and focal keratoderma with painful fissures Superficial peeling of the skin with no obvious blisters
the reduction in melanin density, and result in depigmentation. Further studies on the defective proteins in KS and possible related gene mutations may clarify the mechanism underlying the association of vitiligo. Another unusual feature observed in our patient was the presence of hypodontia and marked dental caries. It was found previously that cytokeratin 5 binds to the amelogenin trityrosyl motif peptide
ª 2014 British Association of Dermatologists
(ATMP) sequence of amelogenin, and is suspected to play a chaperone role for nascent amelogenin polypeptides.9 Thus, keratin mutations are likely to contribute to the enamel defects present in KS. The congenital alopecia in our patient may be related to a possible link between K5 or K14 mutations and hair loss. Tong and Coulombe10 identified K17 and TNF-a as two novel and interdependent
Clinical and Experimental Dermatology (2015) 40, pp35–38
37
Kallin syndrome associated with vitiligo M. A. El Darouti et al.
regulators of hair cycling. They also revealed that K17-null skin keratinocytes in primary culture are selectively more sensitive to TNF-a, and that this occurs via an interaction between K17 and the TNF receptor 1 (TNFR1)-associated death domain protein (TRADD).10 The association of K14 with TNF-a induced apoptosis is still controversial; it is unclear whether this protects from apoptosis via sequestration of TRADD away from TNFR1 (as does K18), or increases apoptosis (as does K17).11 These questions need to be explored further, but the current data point to a possible intimate relationship between K14 (and possibly K17 mutations) and the alopecia observed in KS. Genetic mapping is of prime importance to solve this puzzle and to determine if the mutated keratins in this unique type of EBS are restricted to K5 and K14 only, or if there is an additional mutation of K17, resulting in the multiple associations present in our patient. Unfortunately, genetic study of our patient was not possible.
Learning points KS is an extremely rare variant of EBS. The features associated with KS include
trauma-induced blisters, deafness, alopecia, hypodontia and nail dystrophy. The blisters in EBS occur from birth, developing after trauma and healing without scarring. Skin pigmentation is the result of an intimate partnership between keratinocytes and melanocytes. Multiple genetic findings have formalized a role for keratin in regulating skin pigmentation. Two genetic possibilities for KS have been suggested: an autosomal recessive genetic trait or a gonadal mosaicism with an early dominant gene mutation.
2
3
4
5
6
7
8
9
10
11
nail disorders: a new syndrome. Acta Derm Venereol 1985; 65: 526–30. Fine JD, Eady RA, Bauer EA et al. The classification of inherited epidermolysis bullosa (EB); report of the third International Consensus Meeting on diagnosis and classification of EB. J Am Acad Dermatol 2008; 58: 931– 50. Uttam J, Hutton E, Coulombe PA et al. The genetic basis of epidermolysis bullosa simplex with mottled pigmentation. Proc Natl Acad Sci USA 1996; 93: 9079– 84. Gu LH, Kim SC, Ichiki Y et al. A usual frameshift and delayed termination codon mutation in keratin 5 causes a novel type of epidermolysis bullosa simplex with migratory circinate erythema. J Invest Dermatol 2003; 121: 482–5. Betz RC, Betz RC, Planko L et al. Loss-of-function mutations in the keratin 5 gene lead to Dowling-Degos disease. Am J Hum Genet 2006; 78: 510–19. Lugassy J, Itin P, Ishida-Yamamoto A et al. Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: two allelic ectodermal dysplasias caused by dominant mutations in KRT14. Am J Hum Genet 2006; 79: 724–30. Styers ML, Kowalczyk AP, Faundez V. Intermediate filaments and vesicular membrane traffic: the odd couple’s first dance? Traffic 2005; 6: 359–65. Lugassy J, McGrath JA, Itin P et al. KRT14 haploinsufficiency results in increased susceptibility of keratinocytes to TNF-alpha-induced apoptosis and causes Naegeli-Franceschetti-Jadassohn syndrome. J Invest Dermatol 2008; 128: 1517–24. Ravindranath RM, Basilrose RM Sr, Ravindranath NH, Vaitheesvaran B. Amelogenin interacts with cytokeratin-5 in ameloblasts during enamel growth. J Biol Chem 2003; 278: 20293–302. Tong X, Coulombe PA. Keratin 17 modulates hair follicle cycling in a TNF-a dependent fashion. Genes Dev 2006; 20: 1353–64. Yoneda K, Furukawa T, Zheng YJ et al. An autocrine/ paracrine loop linking keratin 14 aggregates to tumor necrosis factor a-mediated cytotoxicity in a keratinocyte model of epidermolysis bullosa simplex. J Biol Chem 2004; 279: 7296–303.
References 1 Gamborg Nielsen P, Sj€ olund E. Epidermolysis bullosa simplex localisata associated with anodontia, hair and
38
Clinical and Experimental Dermatology (2015) 40, pp35–38
ª 2014 British Association of Dermatologists
This document is a scanned copy of a printed document. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material.
