BJD

C O N CI S E C O M M U N I C A T I ON British Journal of Dermatology

Mutations in KRT5 and KRT14 cause epidermolysis bullosa

simplex in 75% of the patients
M.C. Bolling, H.H. Lemmink,* G.H.L. Jansen* and M.F. Jonkman
Center for Blistering Diseases, Department of Dermatology and *Department of Genetics, University Medical Center Groningen, Hanzeplein 1, 9713 GZ
Groningen, the Netherlands

Summary

Correspondence Background Epidermolysis bullosa simplex (EBS) is a mechanobullous genodermato-

Marieke Bolling. sis that may be caused by mutations in the genes KRT5 and KRT14 encoding the
E-mail: m.c.bolling@derm.umcg.nl basal epidermal keratins 5 (K5) and 14 (K14). Three main clinical subtypes of
EBS exist, differing in onset, distribution and severity of skin blistering. Previous
Accepted for publication
13 November 2010
reports of KRT5 and KRT14 mutations suggest a correlation between the location
of the mutation and the severity of the associated EBS phenotype.
Funding sources Objectives The prevalence of KRT5 ⁄KRT14 mutations and the genotype–phenotype
J.P. Nater Foundation, the Netherlands. correlation in the largest tissue-confirmed EBS population is investigated.
Methods KRT5 and KRT14 genomic DNA and cDNA sequences of 76 clinically well-
Conflicts of interest
defined unrelated EBS probands were amplified and then subjected to direct
None declared.
sequencing and product length analysis. Immunofluorescence microscopy on
DOI 10.1111/j.1365-2133.2010.10146.x patients’ skin biopsies with antibodies against K5 and K14 was performed to
study protein expression.
Results In 57 of 76 (75%) probands 41 different KRT5 and KRT14 mutations were
identified, of which 12 were novel. Mutations affecting the highly conserved
helix boundary motifs of the rod domains of K5 and K14, and the K14 helix
initiation motif in particular, were associated with the severest, EBS Dowling-
Meara, phenotype. In 21 EBS probands (37%) the mutation was de novo. In 19
probands (25%) KRT5 or KRT14 mutations were excluded.
Conclusions The phenotype–genotype correlation observed in this large EBS popula-
tion underscores the importance of helix boundary motifs for keratin assembly.
Only three-quarters of biopsy-confirmed EBS probands have KRT5 or KRT14 muta-
tions, indicating genetic heterogeneity in EBS. Alternative gene candidates are
discussed.

Epidermolysis bullosa simplex (EBS) is the most common
genetic blistering disease with an estimated prevalence of 1 in
25 000–50 000.1–3 EBS is characterized by cleavage through
basal keratinocytes upon minor trauma leading to skin blister-
ing in a range of severity.4 EBS-localized (EBS-loc) is the mild-
est form with onset of blistering in infancy affecting mainly
hands and feet. EBS-generalized non-Dowling–Meara (EBS-
gen) is characterized by generalized blistering usually present
from birth. EBS Dowling–Meara (EBS-DM) is the most severe
subtype with severe neonatal generalized circinary vesicles
often affecting the mucosae as well, with later development of
palmoplantar keratoderma. Other minor subtypes are EBS with
mottled pigmentation (EBS-MP), migratory circinate EBS and
autosomal recessive EBS. EBS is caused mostly by mutations in
KRT5 and KRT14 encoding the basal keratins 5 (K5) and 14
(K14).5–7 K5 and K14 form parallel coiled-coil heterodimers
by means of their a-helical rod domains and further assemble
into a dynamic tonofilament cytoskeleton to provide strength
and flexibility to basal keratinocytes.8–11 Most mutations
affecting the highly conserved helix boundary motifs (HBMs)
of the rod domains of K5 and K14 are associated with the
severe EBS-DM phenotype, while mutations outside these
domains tend to be associated with milder phenotypes (see
http://www.interfil.org12).
Here we present the results of KRT5 and KRT14 mutation anal-
ysis in the largest group of patients with biopsy-proven EBS.
Patients and methods
The study was conducted according to the ethical principles
provided by the Declaration of Helsinki. A total of 76 families
with EBS was identified at the Center for Blistering Diseases in
the Netherlands. The diagnosis was invariably based on clinical
features,4 immunofluorescence antigen mapping (IF) and elec-

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BJD  2011 British Association of Dermatologists 2011 164, pp637–644 637
638 KRT5 and KRT14 mutations in 75% of EBS patients, M.C. Bolling et al.
tron microscopy (EM) analysis revealing a basal cell split. A
clinical diagnosis of EBS-DM was made if at least one of two
features was present: (i) early-onset generalized blistering
with nonmigratory circinate pattern, and (ii) tonofilament
clumping in (supra-)basal cells observed by EM. EBS-gen is
characterized by generalized blistering without circinate pat-
tern or tonofilament clumping. EBS-loc was defined as blister-
ing confined to hands and feet, usually with seasonal
variation, being more severe during summer. EBS-MP is char-
acterized by a mild EBS-gen or an EBS-loc blistering pheno-
type in combination with reticulated hyperpigmentation.
Skin biopsies
Routinely 4-mm (IF13) and 2-mm (EM13) punch biopsies
were taken. For IF antibodies BL18 against K5, LL001 against
K14, 1A8c and 1D1 against BP180, 58XB4 and clone-7 against
integrin b4, GB3 against laminin-332, and LH7.2 against type
VII collagen were used to determine the level of blister forma-
tion and protein expression in basal cells.
Mutation detection
Genomic DNA (gDNA) was extracted from blood from
patients and family members.14 Polymerase chain reaction
(PCR) amplification of exons 1–9 of KRT5 (GenBank
NM_000424.3) and exons 1–8 of KRT14 (GenBank
NM_000526.3) was performed.15,16 PCR products were sub-
sequently purified (Qiagen Quick PCR Purification kit; Qiagen,
Venlo, Netherlands) and directly sequenced (automated
ABI3100 Genetic Analyzer; Applied Biosystems, Foster City,
CA, U.S.A.). Novel KRT5 and KRT14 mutations were excluded
in 100 alleles of control gDNA samples.
RNA analysis
From patients with EBS in whom no KRT5 or KRT14 mutation
was detectable on gDNA, RNA analysis was performed. Per
proband four 10-lm skin cryosections were cut and trans-
ferred with a sterile needle into lysis buffer (Stratagene Eur-
ope, Heidelberg, Germany). RNA was extracted and cDNA
was subsequently synthesized according to protocols provided
by the manufacturer (Absolutely RNA Microprep kit protocol;
Stratagene Europe and Invitrogen, Breda, Netherlands). The
resulting cDNA was PCR amplified with forward primer
sequences located in exon 1 and reverse primer sequences
located in the most 3¢ end of KRT5 and KRT14 cDNA sequences
(Table S1; see Supporting Information). The length of the
amplified cDNA fragments was analysed on 1% agarose gels.
Results
Mutations were identified in 57 of 76 unrelated EBS families
(75%). Forty-one different mutations were found of which 23
(56%) resided in KRT5 and 18 (44%) in KRT14 (Fig. 1,
Table 1). Twelve novel mutations were found. In 21 of 27
BJD  2011 British Association of Dermatologists 2011 164, pp637–644
sporadic probands DNA from both parents was available and
the mutation could be excluded, indicating de novo mutations
(37%). Thirty of 41 mutations were heterozygous missense
mutations (73%). The mutations were excluded in 100 un-
related healthy control alleles and unaffected family members.
The EBS-DM phenotype was clinically clearly discernable in
all 15 probands. The other patients with EBS showed a spec-
trum in disease severity varying from early-onset persistent
generalized blistering, designated EBS gen-nDM, at the one
end, and blistering confined to hands or feet beginning at the
age when the child started to walk, designated EBS-loc, at the
other end of the spectrum. In between are patients with mild
generalized blistering starting from birth, which markedly
improved over the years, so that later in life blistering was
confined to hands and ⁄or feet (Table 1). Palmar or palmo-
plantar keratosis was not only associated with EBS-DM (20%),
but also with EBS gen-nDM (11%) and EBS-loc (55%).
No KRT5 or KRT14 mutations
KRT5 or KRT14 mutations were excluded in 19 EBS probands
(25% of the total sum of EBS families). EBS was confirmed by
cleavage through the basal cell layer in skin biopsy. IF staining
of skin biopsies showed presence of K5 and K14 proteins and
additional RNA analysis of the complete KRT5 and KRT14 tran-
scripts did not indicate heterozygous inframe deletions or
insertions as no additional bands were observed by analysing
the PCR fragments of reverse transcription–PCR on agarose gel
(data not shown). The phenotypes of these 19 non-
KRT5 ⁄KRT14 mutation EBS cases comprised EBS-DM (n = 2),
EBS-gen (n = 2), EBS-MP (n = 1) and EBS-loc (n = 14). Eight
of these 19 probands were sporadic cases.
Discussion
We present the largest series of patients with EBS, with 76
families being characterized at the clinical, histological and
molecular level. In 57 families KRT5 and KRT14 mutation anal-
ysis revealed a total of 41 mutations, of which 12 mutations
are novel. Our main observations were: (i) association of
mutations in mainly the HBMs, and in particular the K14 helix
initiation motif (HIM), with the most severe EBS-DM pheno-
type with keratin clumping in skin; (ii) a high percentage of
sporadic patients with proven de novo mutations (37%); and
(iii) a high percentage (25%) of patients with proven EBS
without mutations in KRT5 or KRT14.
In our patients with EBS with keratin mutations the EBS-DM
phenotype was in all but one (KRT5:p.Ala438Asp) associated
with mutations in the HBMs, in particular the HIM of K14.
This finding fits with previous reports (Fig. 1, http://
www.interfil.org). The sequences in these HBMs are highly
conserved, and play an essential role in the initial dimer–
dimer interactions in filament formation.17–19 The high
frequency of particularly the K14 HIM mutations in EBS-DM
is due to mutations affecting the CpG-rich ‘hotspot’ codon
p.Arg125.20,21 Nevertheless, milder EBS-loc phenotypes were
 2011 The Authors
 KRT5 and KRT14 mutations in 75% of EBS patients, M.C. Bolling et al. 639

(a)

(b)

Fig 1. Schematic representation of keratin 5 (a, K5) and keratin 14 (b, K14) with the nonhelical head domains in light green, the a-helical rod
domains in light blue and the helix boundary motifs in pink. The mutations detected in the present study are illustrated above the protein with
the novel mutations in a box. Below the protein the previously reported mutations are shown (the sum of different mutations with their
associated phenotypes per keratin domain). loc, localized; gen-nDM, generalized non-Dowling–Meara; DM, Dowling–Meara; EBS-AR, autosomal
recessive epidermolysis bullosa simplex. *Frame shift mutations.

also associated with missense mutations in HBMs, like
KRT5:p.Glu170Gly, KRT5:p.Asn177Ser and KRT5:p.Gly476Asp.
Heterodimers like K5-K14 are coiled-coil heptad (abcdefg)n
structures with the keratin polypeptides interacting through
hydrophobic interactions between apolar residues in positions
a and d of the heptad and stabilized by interactions between
hydrophilic residues at positions e and g. It has been suggested
that mutations affecting these positions cause the more severe
phenotypes.22 In our series this was not observed. KRT14
mutations p.Ile412Phe and p.Leu408Met affect positions a and
d of the heptad repeat structure, but both result in the mild
EBS-loc phenotype, and mutation p.Glu475Lys involving
position b in the heptad structure caused severe EBS-DM in
another patient (Table 1). Most likely the position of the
substituted amino acid in the local structure of the protein, in
combination with the physical-chemical nature of the amino
acid change, determine the effect of the mutation on protein
functioning, filament assembly, and ultimately the phenotype.
In addition, other factors (environmental, epigenetic, genetic
background) may govern the clinical outcome as well.
This study revealed a high rate (37%) of de novo mutations.
Nonpaternity or germline mosaicism may be underlying some
of the seemingly de novo mutations. Alternatively, hardly any
changes in the highly conserved keratins are tolerated and
therefore any change results in disease phenotype. Thus, the
high percentage of de novo events may reflect a high mutability
at this part of the human genome during reproduction. The
three codons more prevalently affected by mutations in multi-
ple families in this study, KRT14:p.Arg125 (n = 5 families),
KRT14:p.Arg388 (n = 3 families) and KRT5:p.Arg187 (n = 4

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BJD  2011 British Association of Dermatologists 2011 164, pp637–644
 Table 1 Phenotypes and KRT5 and KRT14 genotypes of the epidermolysis bullosa simplex (EBS) families reported in this study

Additional Clinical
Mutation EBS Onset clinical intrafamial EM: Phenotype in previous
Families Gene (c.)a Mutation (p.)a Domain Heptad Origin Inheritance subtype blistering features variability clumping Published inb reports
1 EB057, KRT5 74C>T Pro25Leu V1 NA Dutch AD (2·), MP Variable Pitted PPK, Yes No Moog, 199934 MP (Uttam, 199635)c
EB060, Sp (4·) (birth–6 teeth
EB110, years)
EB237,
EB241,
EB242
2 BE03 KRT5 446T>C Leu149Pro H1 NA Belgian AD loc Birth Nails No No
3 EB135 KRT5 451A>C Thr151Pro H1 NA Dutch AD loc 1 year None No No
4 EB190 KRT5 509A>G Glu170Gly 1A (HIM) f M-E Sp > AD loc 1 year PPH No No gen-nDM (Rugg, 200723)
5 EB179 KRT5 530A>G Asn177Ser 1A (HIM) f Dutch AD loc Variable PPH Yes No loc (Liovic, 200436)
(birth–> 10
years)
6 EB201 KRT5 539C>A Ala180Asp 1A (HIM) b M-E Sp gen Birth Aplasia cutis NA No DM (Hamada, 200537)
7 EB209 KRT5 538G>C Ala180Pro 1A (HIM) b Dutch AD DM Birth PPK, nails, teeth, No Yes
compound naevi
8 EB080 KRT5 556-1G>C Val186_Gln189del 1A NA Dutch Sp gen Birth Focal PPK, nails NA No Schuilenga-Hut,
200315
9 EB038, KRT5 560G>C Arg187Pro 1A b Dutch AD (4·) loc 1 year PK No No
EB094,
EB136,
640 KRT5 and KRT14 mutations in 75% of EBS patients, M.C. Bolling et al.

EB144
10 EB213 KRT5 572A>C Gln191Pro 1A f Korean Unknown gen Unknown PPK Unknown Unknown gen (Yasukawa, 200638;
Glasz-Bona, 200939)
11 EB197 KRT5 596A>T Lys199Met 1A g Indian AD loc Birth PK No No
12 BE02 KRT5 968T>G Val323Gly L12 NA Belgian Sp loc Unknown PK NA No
13 EB195 KRT5 987C>A Asn329Lys L12 NA Finnish AD loc 1 year PK No No loc (Chan, 199440)
14 EB182 KRT5 992G>A Arg331His L12 NA Dutch AD loc 1 year None No No loc (Muller, 200622;
Kang, 201041)
15 EB063 KRT5 1210A>G Lys404Glu 2B e Dutch AD loc 1 year None No No Schuilenga-Hut,
200315
16 EB073 KRT5 1313C>A Ala438Asp 2B g Dutch Sp DM Birth PPK NA Yes Schuilenga-Hut,
200315
17 EB137 KRT5 1329G>C Lys443Asn 2B e Dutch AD loc Variable PPK, PPH Yes No
18 EB116 KRT5 1401C>G Ile467Met 2B (HTM) a Dutch Spd gen Birth PPH, nails Yes No gen-nDM
(Pfendner, 200542)
19 EB054 KRT5 1423G>A Glu475Lys 2B (HTM) b Dutch Sp > AD DM Birth PPK, nails No Yes Schuilenga-Hut, DM (Yasukawa, 200638)
200315
20 EB166 KRT5 1427G>A Gly476Asp 2B (HTM) c Dutch AD loc 1 year No No loc (Abu Sa’d, 200643)
21 EB259, KRT5 1474+4A>G Unknown 2B ⁄ V2 NA Dutch AD loc 10 years PK No No
EB264 (intron 8)
22 EB218 KRT5 1635delG Leu546SerfsX82 V2 NA Dutch Sp > AD gen Birth PPK, nails No No loc (Sprecher, 200344)

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BJD  2011 British Association of Dermatologists 2011 164, pp637–644
 Table 1 (Continued)

Additional Clinical
Mutation EBS Onset clinical intrafamial EM: Phenotype in previous
Families Gene (c.)a Mutation (p.)a Domain Heptad Origin Inheritance subtype blistering features variability clumping Published inb reports
23 BE01 KRT5 1649delG Gly550AlafsX77 V2 NA Belgian AD MCE (?) Birth Migratory No No MCE (Gu, 200345;

 2011 The Authors

vesicles on Nagao-Watanabe, 200446),
erythematous MP (Horiguchi, 200547)
skin
24 EB223 KRT14 368A>G Asn123Ser 1A (HIM) e Spain Sp DM Birth PPK, nails NA Yes DM (Sorensen, 199948;
Pfendner, 200542)
25 EB019, KRT14 373C>T Arg125Cys 1A (HIM) g Dutch (3·), Sp (4·) DM Birth PPK, nails NA Yes DM (Coulombe, 19915)c
EB053, M-E (1·)
EB075,
EB153
26 EB046 KRT14 374G>C Arg125His 1A (HIM) g Dutch AD DM Birth PPK, nails No Yes DM (Coulombe, 19915)c
27 EB164 KRT14 383_385 p.Ser128del 1A (HIM) c Dutch Sp DM Birth PPK, nails NA Yes DM (Wood, 200349)
delTCC
28 EB105 KRT14 389T>C Leu130Pro 1A (HIM) e M-E Sp DM Birth PPK, nails NA Yes Schuilenga-Hut,
200315
29 EB014, KRT14 526-2A>C [Ile176ValfsX2] + 1B NA Dutch AR (3·) AR Birth PPK, generalized Yes No Jonkman, 199650;
EB067, [Ile176ProfsX30] hyperkeratotic Schuilenga-Hut,
EB070 plaques 200251
30 EB108 KRT14 740_748 Ala247_Lys250 1B NA Dutch AD loc 1 year None No No

BJD  2011 British Association of Dermatologists 2011 164, pp637–644

del9ins3 delinsGlu
31 EB253 KRT14 815T>G Met272Arg L12 Dutch AD DM Birth PPK No Yes gen (Humphries, 199352)
32 EB096 KRT14 927+1G>T ? L2 ⁄ 2B NA Dutch Sp > AD loc Birth PK Yes No
33 EB128 KRT14 927+1G>A ? L2 ⁄ 2B NA Dutch Sp loc Birth PK NA No Schuilenga-Hut, loc (Han, 200653)
200315
34 EB160 KRT14 1130T>A Ile377Asn 2B a Dutch Sp loc 1 year None NA No loc (Chen, 199554)
35 EB226 KRT14 1130T>C Ile377Thr 2B a Dutch AD loc 1 year PK No No loc (Rugg, 200723)
36 EB150, KRT14 1162C>T Arg388Cys 2B e Dutch AD (3·) loc Variable PK, nails Yes No loc (Chen, 199554;
EB157, (birth–2 Rugg, 200723; Glasz-Bona,
EB165 years) 200939; Kang, 201041)
37 EB095 KRT14 1222C>A Leu408Met 2B d Dutch Sp loc 3 years Nails NA No Schuilenga-Hut,
200315
38 EB115 KRT14 1231_1233 Glu411del 2B g Dutch Sp > AD loc 1 year None No No loc (Muller, 200622;
delGAG Jerabkova, 201055
39 EB167 KRT14 1234A>T Ile412Phe 2B a M-E AD loc 3 years PPK No No
40 EB205 KRT14 1240_1249 p.Thr414AlafsX25 2B ⁄ V2 NA Dutch Sp gen Birth Aplasia cutis, NA No
del10 nails, oral
41 EB069 KRT14 1256T>A Leu419Gln 2B (HTM) a Dutch Sp > AD DM Birth PPK, nails Yes Yes Hut, 200056;
Schuilenga-Hut,
200315

a
Nucleotide numbering: +1 corresponds to the A of the ATG translation initiation codon in the reference sequence (RefSeqs KRT5: NM_000423.5, KRT14: NM_000526.3). bPublished in: some of the patients ⁄ families in
this study have been previously reported: reference is given. cFirst publication of this mutation. dTwo affected sisters with unaffected parents not carrying the mutation: possibly germline mosaicism. AD, autosomal
dominant; AR, autosomal recessive; DM, Dowling–Meara; EM, electron microscopy; gen, generalized; gen-nDM, generalized non-Dowling–Meara; HIM, helix initiation motif; HTM, helix termination motif; loc, local-
ized; MCE, migratory circinate erythema; M-E, Middle-East; MP, mottled pigmentation; NA, not applicable; nails, nails affected; oral, oral mucosal erosions; PK, plantar keratoderma; PPH, palmoplantar hyperhidrosis;
PPK, palmoplantar keratoderma; Sp, sporadic; teeth, teeth abnormalities.
KRT5 and KRT14 mutations in 75% of EBS patients, M.C. Bolling et al. 641
642 KRT5 and KRT14 mutations in 75% of EBS patients, M.C. Bolling et al.
families), contain the highly mutable CpG dinucleotide.21 The
four Dutch families with KRT5:p.Arg187Pro might share a
common founder.
Similar to the 22% in the EBS population in the U.K.,23 we
found 25% of patients with EBS without mutations in the
KRT5 or KRT14 genes. The strength of our study lies in the
confirmation of an intraepidermal split in the patient’s skin,
thereby providing definitive diagnosis of EBS. The complete
coding sequences of KRT5 and KRT14 were analysed and we
excluded autosomal recessive null mutations by showing unre-
duced expression of both proteins by IF. Larger deletions or
duplications were excluded by RNA analysis. Of note, smaller
insertions or deletions will be missed, but these are expected
to be found by the amplification and sequencing of single
exons with their exon–intron borders. K5 or K14 haploinsuffi-
ciency is unlikely as this causes other phenotypes (Dowling–
Degos disease, Naegeli–Franceschetti–Jadassohn syndrome and
dermatopathia reticularis pigmentosa).24,25 Altogether, this
indicates that other genes besides KRT5 and KRT14 may be
involved in a significant portion of EBS.
Other genes besides KRT5 and KRT14 have been associated
with basal intraepidermal skin blistering in single patients or
families and ⁄or are possible candidate genes on the basis of
their localization: PLEC (plectin), ITGB4 (integrin b4),
COL17A1 (type XVII collagen) and DST (BP230). Keratin 15 is
another keratin besides K5 and K14 that is expressed in basal
keratinocytes, and this protein may form heterodimers with
K5 as well. Rugg et al. searched for mutations in KRT15 in their
mutation-negative EBS cases and Kemp did the same in an EBS
patient cohort from Australia and New Zealand, but neither
found a mutation in this gene.23,26 Another possible explana-
tion for fragility of the basal keratin skeleton could be a defec-
tive protein involved in keratin assembly, elongation and ⁄or
functioning, like for example proteins influencing the phos-
phorylation of keratins which in turn affect the polymerization
status.27,28 Alternative explanations for KRT5 and KRT14 muta-
tion-negative EBS could lie in epigenetic phenomena, like for
example paramutation.29–31
In conclusion, our data implicate that EBS due to mutations
in KRT5 and KRT14 is not clinically discernable from pheno-
types caused by mutations in other genes. Considering the
similar phenotype and mode of inheritance (EBS-Ogna) associ-
ated with a previously reported plectin missense mutation we
propose PLEC as a first candidate.32,33
What’s already known about this topic?
• Epidermolysis bullosa simplex (EBS) is caused by muta-
tions in the keratin 5 (KRT5) or keratin 14 (KRT14)
genes and shows a wide spectrum of disease severity.
• Identification of novel mutations aids in the understand-
ing of the phenotype–genotype correlation in EBS and is
important for adequate patient management and coun-
selling from an early age.
BJD  2011 British Association of Dermatologists 2011 164, pp637–644
What does this study add?
• The largest population of biopsy-proven patients with
EBS with the disease-causing mutations presented thus
far.
• Twelve novel mutations in KRT5 and KRT14.
• In this study it is shown that 75% of EBS, in biopsy-
proven patients, is caused by mutations in the
KRT5 ⁄KRT14 genes.
• We show that 25% of EBS cases are not caused by KRT5
or KRT14 mutations; alternative explanations are dis-
cussed.
• EBS not due to mutations in KRT5 ⁄KRT14 is clinically
indiscernible from EBS due to KRT5 ⁄KRT14 mutations.
Acknowledgments
We are grateful to the patients and their families who partici-
pated in this study. We thank Prof. E. Legius (Department of
Human Genetics, Catholic University Leuven, Leuven, Bel-
gium) and Dr. M. Morren (Department of Dermatology, Cath-
olic University Leuven, Leuven, Belgium) for providing DNA
samples and clinical data from three patients (BE01, BE02 and
BE03) with EBS.
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Supporting Information
Additional Supporting Information may be found in the online
version of the article:
Table S1 Primer sequences and conditions for polymerase
chain reaction amplification of KRT5 and KRT14 cDNA
sequences.
Please note: Wiley-Blackwell are not responsible for the
content or functionality of any supporting materials supplied
by the authors. Any queries (other than missing material)
should be directed to the corresponding author for the article.
 2011 The Authors