Correspondence
I. H. Bucak1, H. Almis1 and M. Turgut2
Departments of 1 Pediatrics and 2Pediatric Infectious Disease,
Adiyaman University School of Medicine, Altınsßehir Neighborhood,
Uygur site, G-Bloc No. 32, 02040, Adiyaman, Turkey
E-mail: ihbucak@hotmail.com
Conflict of interest: the authors declare that they have no conflicts of
interest.
Accepted for publication 21 April 2017
References
1 Na SY, Son YM, Lee HY et al. A case of varicella
combined with hand-foot-mouth disease in a healthy
child. Ann Dermatol (Seoul) 2009; 21: 98–101.
2 Siadat AH, Nilforoush Zadeh MA, Moradi SH et al.
Localization of varicella around cutaneous leishmaniasis.
Indian J Dermatol Venereol Veprol 2007; 73: 124–6.
3 Nagore E, Sanchez-Motilla JM, Julve N et al. Atypical
involvement of palms and soles in a varicella infection.
Acta Derm Venereol 1999; 79: 322.
4 T€ € T€
ursen U, ursen B. Dermatolojide ‘‘ps€odo’’ durumlar.
Dermatoz 2013; 4: 101–10.
5 Belhorn TH, Lucky AW. Atypical varicella exanthems
associated with skin injury. Pediatr Dermatol 1994; 11:
129–32.
A recurrent mutation in the KRT17 gene responsible
for severe steatocystoma multiplex in a large
Chinese family
doi: 10.1111/ced.13311
Steatocystoma multiplex (SM; OMIM 184500) is a rare
autosomal dominant cutaneous disorder, which is charac-
terized by multiple cutaneous nodules of variable size,
Figure 1 Pedigree of a Chinese family with steatocystoma multiplex. Arrow indicates the proband.
ª 2017 British Association of Dermatologists
and is most commonly found on the sternal areas, upper
extremities, face and anterior trunk. The lesions usually
start to develop in adolescence or early adult life.1 These
nodules may present as an isolated feature, and can also
be found in conditions such as pachyonychia congenita
type II, LEOPARD syndrome and Alagille syndrome.1–3
SM results from a mutation of the keratin 17 gene
(KRT17; OMIM 148069) within the type I keratin cluster
on chromosome 17q21.2.4 Keratin 17 is expressed in the
sebaceous glands, nail bed, hair follicle and other epider-
mal appendages5. In the present work, we report a recur-
rent KRT17 gene mutation responsible for severe
steatocystoma multiplex in a Chinese family.
In this study, we investigated a four-generation family
from Henan province in China. The family was comprised
of 40 individuals, including 7 with typical severe SM
features (Fig. 1). The condition showed an autosomal
dominant inheritance pattern with full penetrance. The
proband (II:10 in the pedigree) was a 53-year-old man
who had a history of subcutaneous nodules, varying in size
from 2–80 mm, over almost his whole body since puberty.
The numbers of lesions had gradually increases in diameter
with age (Fig. 2a–e). Multiple subcutaneous nodules were
fluctuating but not painful. No inflammation was found.
Histological examination of a lesional skin biopsy from
a 10-mm cyst on the patient’s right forearm revealed an
unfolded round cystic wall and the absence of a granular
layer. Sebaceous gland lobules were adjacent to the cyst
lining (Fig. 2f).
All affected individuals in this family had similar mani-
festations, but the proband’s brothers (II:7 and II:11) pre-
sented milder clinical features. The proband’s condition
was the most severe in the family. None of the affected
individuals had any evidence of nail changes, plantar ker-
atoderma or plantar pain, or any other skin, hair, sweat
or mucosal abnormalities.
Clinical and Experimental Dermatology (2018) 43, pp191–208 205
Correspondence

(a) (b) (c)

(d) (e) (f)

(g)

(h)

Figure 2 Clinical characteristics of the proband: multiple subcutaneous nodules on (a) the upper trunk and shoulders (b) back, shoulders
and buttocks, (c) arms, (d) legs, and (e) face and head. (f) Histology showed an unfolded round cystic wall and the absence of a granular
layer, while sebaceous gland lobules were adjacent to the cyst lining ((haematoxylin and eosin, original magnification 9 40. (g) Mutation
analysis of the KRT17 gene showed a heterozygous transition mutation c.280 C>T, resulting in the missense mutation p.Arg94Cys; (h)
part of the normal sequence from exon q of the KRT17 gene, with the red arrow indicating the mutation in this family.

206 Clinical and Experimental Dermatology (2018) 43, pp191–208 ª 2017 British Association of Dermatologists

Table 1 Primer sequences used in this study.
Primer direction Sequence 50 ?30
Forward ATGGAAACAGAGGAGCA
Reverse CCTGACTCAGCTTGCTGT
We carried out a genetic study on the family. The
study was approved by the ethics committee of Henan
Provincial People’s Hospital, and conducted in accordance
with the principles of the Declaration of Helsinki. All par-
ticipants provided informed consent.
Peripheral blood was collected from each participant.
Genomic DNA was extracted from lymphocytes and used
as a template for PCR amplification. The primer
sequences are shown in Table 1. The DNA template
(100 ng) was mixed in a solution containing 19 PCR
buffer, consisting of 100 mmol/L Tris-HCl (pH 8.3) and
500 mmol/L KCl, 1.5 mmol/L MgCl2, 50 lmol/L dNTPs,
10 pmol of each primer, and 2.5 U of Taq DNA poly-
merase (Promega Corporation, Madison, WI, USA), in a
final reaction volume of 30 lL. Amplification was per-
formed using an initial denaturation at 95 °C for 1 min,
followed by 35 cycles of denaturing at 95 °C for 40 s,
annealing at 58 °C for 40 s and extension at 72 °C for
1 min, with a final extension at 72 °C for 3 min. The
resulting product was sequenced on an automated
sequencer (ABI PRISM 3730; Applied Biosystems, Foster
City, CA, USA). Sequence comparisons and analysis
were performed using Phred-Phrap-Consed program
(v12.0; http://www.phrap.org/phredphrapconsed.html), and
mutations were identified by comparing the sequence
with the reported cDNA reference sequence (GenBank
accession no. NM_000422.2).
Mutation analysis of the proband’s genomic DNA
revealed a recurrent mutation, c.280C>T (p.Arg94Cys), in
the KRT17 gene (Fig. 2g,h), which is the hotspot mutation
for SM. This mutation segregated clearly with the disease
phenotype within the family members, and it was not
detected in 100 unrelated healthy Chinese individuals.
SM is a rare genetic skin disease that usually presents
in adolescence. It always presents with multiple cuta-
neous cysts on the trunk, axilla, groin and proximal
extremities because of the high density of the developed
pilosebaceous units. The multiple cutaneous lesions are
generally 1–20 mm in size.6 SM lesions occurring as mul-
tiple nodules > 20 mm in size are very rare.6 Jeong et al.
reported a patient with four cystic masses varying in size
from 10 to 40 mm and located on the scalp.6 Yonekura
et al. also reported a giant steatocystoma, around 60 mm
in size, which was located on the patient’s scalp.7 Our
case is interesting in that the proband had multiple nod-
ules varying in size from 20 to 80 mm on the face, trunk
and proximal extremities.
In the current study, we identified a heterozygous mis-
sense mutation c.280 C>T (p.Arg94Cys) in the 1A domain
ª 2017 British Association of Dermatologists
Correspondence
of the KRT17 gene. The possible arginine substitution can
result from deamination mutation of this codon. This
mutation is predicted to be detrimental to the keratin
cytoskeleton, producing cell fragility and hyperkeratosis in
tissues expressing dkeratin 17,8 and it has been reported
previously in several families with SM or pachyonychia
congenita type 2.8,9 In our family, the patients had severe
typical epidermal cysts, but no changes in mucous mem-
branes, hair or nails. SM was the only phenotype found.
Compared with the patients reported previously, all affected
members with SM in this family have a more severe form.
The same mutation will lead to different phenotypes even
in the same family, which suggests that the genotype–
phenotype correlation of SM may be determined not only
by the site and type of the KRT17 gene mutation, but also
by other modifying factors, androgenic stimulation and
even environmental factors.10
In conclusion, we report a recurrent mutation in the
KRT17 gene found in a family with severe SM, which
provides further evidence that some factors such as modi-
fiers, androgenic stimulation and/or environment influ-
ence the phenotypes, and other genetic or proteomic
conditions might also influence the final manifestations of
the disease.
Acknowledgements
We thank all subjects for their ongoing participation in
this study. This study was funded by grants from the
National Nature Science Foundation of China (81472867)
and Shanghai Municipal Education Commission-Gaofeng
Clinical Medicine Grant Support (20161417).
J. Wang1,2, J. Li1,2, X. Li1,2, D. Lei1,2, W. Xiao3, Z. Li1,2,
S. Zhang1,2 and M. Li4
Departments of 1Dermatology and 3 Cardiology, Henan Provincial
People’s Hospital, Zhengzhou, Henan, China; 2Department of
Dermatology, Zhengzhou University People’s Hospital, Zhengzhou,
Henan, China; and 4Department of Dermatology, Xinhua Hospital,
Shanghai Jiaotong University School of Medicine, 1665 Kongjiang
Road, Shanghai, 200092, China
E-mail: aypyslm@163.com
Conflict of interest: the authors declare that they have no conflicts of
interest.
JW and JL contributed equally to this work, and should be considered
joint first authors.
ML and SZ contributed equally to this work, and should be considered
joint senior authors.
Accepted for publication 17 April 2017
References
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J Eur Acad Dermatol Venereol 2009; 23: 723–4.
ª 2017 British Association of Dermatologists