Download Delayedonset pachyonychia congenita caused by a novel mutation

15 March 2005
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Letters to the Editor
skin hypopigmentation despite similar mechanisms. One
explanation for the discrepancy relates to the degree of
effect on various tissues to the target-specificity of imatinib
because different tissues may have diverse c-kit isotypes.5
Our patient showed graying of more than 50% of the scalp
and pubic hair with generalized skin hypopigmentation, but
the rest of the hairs were not involved. This may suggest
that imatinib has target-specificity or a varying degree of ckit inhibition not only between skin and hair but also
between each hair. Besides hair graying, our patient also
showed diffuse hair loss of the scalp, which is also a possible side-effect of imatinib. It is associated with plateletderived growth factor receptor (PDGFR)-regulated maintenance of the anagen phase of the hair cycle.1 The hair loss
is thought to be related to inhibition of PDGFR by imatinib
with resulting telonization of the hair follicles that eventually
led to telogen effluvium.
Both hair graying and hair loss are stressful for young
female patients on antitumor therapy. Therefore, physicians
should be aware of hair graying as an additional possible sideeffect of imatinib and notify patients.
CONFLICT OF INTEREST:
None.
Seok Kweon YUN,1,3 Ki Hun SONG,1
Su Ran HWANG,1 Han Uk KIM,1,3 Na Ri LEE,2,3
Jin PARK1,3
1
Departments of Dermatology, 2Internal Medicine, Chonbuk National
University Medical School, and 3Research Institute of Clinical Medicine of
Chonbuk National University, Biomedical Research Institute of Chonbuk
National University Hospital, Jeonju, Korea
doi: 10.1111/1346-8138.12342
REFERENCES
1 Mariani S, Abruzzese E, Basciani S, Fiore D. Reversible hair depigmentation in a patient treated with imatinib. Leuk Res 2010; 35: e64–
e66.
2 Balagula Y, Pulitzer MP, Maki RG, Myskowski PL. Pigmentary
changes in a patient treated with imatinib. J Drugs Dermatol 2011;
10: 1062.
3 Joensuu H, Trent JC, Reichardt P. Practical management of tyrosine
kinase inhibitor-associated side effects in GIST. Cancer Treat Rev
2011; 37: 75–88.
4 Etienne G, Cony-Makhoul P, Mahon F-X. Imatinib mesylate and gray
hair. N Engl J Med 2002; 347: 446.
5 Campbell T, Felsten L, Moore J. Disappearance of lentigines in a
patient receiving imatinib treatment for familial gastrointestinal stromal tumor syndrome. Arc Dermatol 2009; 145: 1313.
Delayed-onset pachyonychia congenita caused by a novel
mutation in the V2 domain of keratin 6b
Dear Editor,
Pachyonychia congenita (PC) consists of a group of rare autosomal-dominant ectodermal disorders characterized predominantly by nail dystrophy. There are two main clinical subtypes
of PC: PC-1 is caused by mutations in keratin 6a (K6a) gene or
keratin 16 (K16) gene, accompanied by nail dystrophy, severe
palmoplantar keratoderma and oral leukokeratosis; and PC-2 is
linked to mutations in the keratin 6b (K6b) gene or keratin 17
(K17) gene, associated with nail dystrophy, focal palmoplantar
keratoderma and multiple steatocysts.1
A 9-year-old Chinese female was affected by thickened fingernails and toenails at 6 years of age. Physical examination
showed hyperkeratotic fingernails and toenails (Fig. 1a,b). Steatocystoma multiplex, palmoplantar keratoderma and natal
teeth were not found in this patient. Repeated fungal examination under a microscope and culture excluded onychomycosis.
There were no other family members affected by this disease.
Following written informed consent, genomic DNA of the
proband, her parents, and 100 unrelated and unaffected people was extracted from peripheral blood. Direct sequencing of
DNA from the patient revealed a heterozygous 1495G?A
(a)
(b)
(c)
(d)
Figure 1. (a,b) Photograph of the thickened fingernails. (c)
Direct sequencing of the k6b gene. A heterozygous missense
mutation 1495G?A (arrow), which predicts the amino acid
change glycine to serine at codon 499 (G499S) was found. (d)
Sequence in normal subjects.
Correspondence: Shengxiang Xiao, Ph.D. and Songmei Geng, Ph.D., Department of Dermatology, Second Affiliated Hospital of Xi’an Jiaotong
University, 157 Xiwu Road, Xi’an, Shaanxi 0086-710004, China. Email: [email protected] and [email protected]
108
© 2013 Japanese Dermatological Association
Letters to the Editor
mutation in exon 9 of the K6b gene, in the tail domain, leading
to the substitution of glycine 499 by serine (G499S; Fig. 1c).
No mutations were found in K17, K16, K6a or K6c. No such
mutation was found in her parents and the 100 unrelated
controls (Fig. 1d).
Three mutations have been reported in K6b, but this is the
first mutation to be reported in the tail domain of PC-2.
Another known similar mutation was a insertion mutation
located in the tail domain of K6a in PC-1.2 Unlike epidermolysis
bullosa simplex, the correlation between severity of disease
and the location of the mutation within the keratin molecule of
PC is not clear. Connors et al.3 detected a case of late-onset
PC association with a mutation K354N in the central 2B
domain of K16. Our group has reported a mutation N109D in
the second half of the 1A domain of K17 with delayed onset
PC-2.4 Terrinoni et al.5 reported a postzygotic mutation in the
V1 domain of K16 with unilateral palmoplantar nevus and
delayed onset PC-1. In this report, we found a mutation in the
V2 domain of K6b associated with late onset and milder thickened nails. The patients listed above had delayed-onset PC,
the milder phenotypes, and their mutation located at the less
critical site of the keratins which is consistent with Connors
et al. and Xiao et al.’s speculation.3,4
In conclusion, we reported a Chinese female affected with
delayed-onset PC-2 caused by a novel mutation in the K6b
V2 domain. The more PC patients that are reported, the more
clinical data is accumulated. It will help expand the understanding of relationship between genotype and phenotype in
PC and may give some clues to the cause of the phenotypic
variability.
ACKNOWLEDGMENTS:
We thank the patient and her family
for their participation in this report. The authors declare that there was
no funding.
CONFLICT OF INTEREST:
The authors have no conflict of
interest to declare.
Kun GUO, Shengxiang XIAO, Songmei GENG,
Yiguo FENG, Dingwei ZHANG, Pengjun ZHOU,
Yanfei ZHANG
Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong
University, Xi’an, China
doi: 10.1111/1346-8138.12349
REFERENCES
1 Vishakha MS, Sarah LS. A novel mutation in K6b in pachyonychia
congenita type 2. J Invest Dermatol 2007; 127: 2060–2062.
2 Wilson NJ, Leachman SA, Hansen CD et al. A large mutational study
in pachyonychia congenita. J Invest Dermatol 2011; 131: 1018–1024.
3 Connors JB, Rahil AK, Smith FJD, Mclean WHI, Milstone LM.
Delayed onset pachyonychia congenita associated with a novel
mutation in the central 2B domain of keratin 16. Br J Dermatol 2001;
144: 1058–1062.
4 Xiao SX, Feng YG, Ren XR et al. A Novel mutation in the second half of
the keratin 17 1A domain in a large pedigree with delayed-onset pachyonychia congenita type 2. J Invest Dermatol 2004; 122: 892–895.
5 Terrinoni A, Puddu P, Didona B et al. A mutation in the V1 domain of
K16 is responsible for unilateral palmoplantar verrucous nevus.
J Invest Dermatol 2000; 114: 1136–1140.
Generalized granuloma annulare after bacillus Calmette–
rin vaccination, clinically resembling papular tuberculid
Gue
Dear Editor,
rin (BCG) vaccine contains a live,
The bacillus Calmette–Gue
attenuated strain of bovine tuberculin bacteria Mycobacterium
bovis. BCG vaccination has appeared to protect young children from more serious forms of tuberculosis. Real incidence
of complications caused by BCG vaccination have been difficult to ascertain, but are extremely low in spite of the great
number of vaccinations performed. Skin complications vary
from local reactions to disseminated BCG infections.1 Herein,
we report a 3-month-old boy with a complication of generalized granuloma annulare (GGA) mimicking papular tuberculid
after BCG vaccination.
A 3-month-old boy was referred to our dermatology clinic
because of generalized eruptions after BCG vaccination. The
boy was a full-term baby and had no specific past and family
history including tuberculosis. He received a BCG vaccination
on his right arm 1 month after birth. He presented multiple
small erythematous papules, plaques and crusts on the face,
trunk and extremities symmetrically without symptoms occurring 7 weeks after BCG vaccination. The BCG injection site
also showed papular lesions (Fig. 1a–c). On physical examination, no abnormal lymphadenopathy was seen and the overall
clinical features were similar to popular tuberculid. Routine
blood and biochemical tests as well as chest X-ray did not
show any abnormal findings. QuantiFERON-TB Gold using
serum and tuberculin skin test with purified protein derivative
of tuberculin were negative. Histopathology showed a feature
of chronic palisading granulomatous inflammation with central
necrosis and suppuration(Fig. 1d,e). Multiple foci of inflammation with a central core of collagen degeneration surrounded
Correspondence: Eung Ho Choi, M.D., Ph.D., Department of Dermatology, Yonsei University Wonju College of Medicine, 162 Ilsan-dong,
Wonju 220-701, Korea. Email: [email protected]
© 2013 Japanese Dermatological Association
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