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15 March 2005 Use of Articles in the Pachyonychia Congenita Bibliography The articles in the PC Bibliography may be restricted by copyright laws. These have been made available to you by PC Project for the exclusive use in teaching, scholarship or research regarding Pachyonychia Congenita. To the best of our understanding, in supplying this material to you we have followed the guidelines of Sec 107 regarding fair use of copyright materials. That section reads as follows: Sec. 107. - Limitations on exclusive rights: Fair use Notwithstanding the provisions of sections 106 and 106A, the fair use of a copyrighted work, including such use by reproduction in copies or phonorecords or by any other means specified by that section, for purposes such as criticism, comment, news reporting, teaching (including multiple copies for classroom use), scholarship, or research, is not an infringement of copyright. In determining whether the use made of a work in any particular case is a fair use the factors to be considered shall include - (1) the purpose and character of the use, including whether such use is of a commercial nature or is for nonprofit educational purposes; (2) the nature of the copyrighted work; (3) the amount and substantiality of the portion used in relation to the copyrighted work as a whole; and (4) the effect of the use upon the potential market for or value of the copyrighted work. The fact that a work is unpublished shall not itself bar a finding of fair use if such finding is made upon consideration of all the above factors. We hope that making available the relevant information on Pachyonychia Congenita will be a means of furthering research to find effective therapies and a cure for PC. 2386 East Heritage Way, Suite B, Salt Lake City, Utah 84109 USA Phone +1-877-628-7300 • Email—[email protected] www.pachyonychia.org 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 109