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Hermansky–Pudlak syndrome type 4: The second case in Japanese
Abstracts / Journal of Dermatological Science 84 (2016) e89–e180
P13-17[O2-48] Hermansky–Pudlak syndrome type 4: The second case in Japanese Yuta Araki 1,∗ , Yoshiyuki Ishii 2 , Yuko Abe 1 , Junko Yoshizawa 1 , Fumiki Okamoto 3 , Yutaka Hozumi 1 , Tamio Suzuki 1 1
Department of Dermatology, Yamagata University School of Medicine, Yamagata, Japan 2 Department of Dermatology, Tsukuba University School of Medicine, Ibaraki, Japan 3 Department of Ophthalmology, Tsukuba University School of Medicine, Ibaraki, Japan Hermansky–Pudlak syndrome (HPS), a rare autosomal recessive disorder, is characterized by oculocutaneous albinism (OCA), bleeding tendency due to platelet storage pool deficiency and lysosomal accumulation of ceroid-lipofuscin. HPS4 is rare among Japanese people, and only one family with this form has been reported. We report a novel mutation in HPS4 in a HPS patient. This is the second reported case of HPS4 in a Japanese person. The patient was a 6-year-old Japanese girl with OCA. She had typical features such as white/pink skin with no apparent tanning ability, blond hair, light gray irides with nystagmus, and some purpura on her lower limbs. The purpura on her lower limbs had gradually increased, and her hair had recently turned from slightly yellow to blond. Fundoscopy showed hypopigmentation, translucent choroidal blood vessels and underdeveloped yellow spots, compared to the healthy control. The patient also had poor eyesight. Although there was no abnormality in the number of platelets or coagulation factors, her bleeding time was slightly prolonged (>5 min), suggesting a storage pool deficiency. We first screened the patient’s genomic DNA (extracted from peripheral blood) for mutations in the genes responsible for OCA1-4, and HPS1 that has been detected among Japanese people. However, no mutations were detected. We then screened the HPS3 and HPS4 genes by the polymerase chain reaction-single-strand conformation polymorphism and direct sequencing methods, because the patient showed a mild bleeding tendency. A novel homozygous mutation (c.730 C > T, p.Q244X) in exon 10 of the HPS4 gene was detected. There was no pathological mutation in the patient’s HPS3 gene. From these results, we diagnosed her as having HPS4. http://dx.doi.org/10.1016/j.jdermsci.2016.08.527 P13-18[O2-49] IMP-3 expression predicts unfavorable prognosis in acral lentiginous melanoma Yi-Shuan Sheen 1,2,∗ , Yi-Hua Liao 1 , Hsien-Ching Chiu 1 , Shiou-Hwa Jee 1 , Yih-Leong Chang 2 , Chia-Yu Chu 1 1 Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan 2 Graduate Institute of Pathology, College of Medicine, National Taiwan University and Department of Pathology, National Taiwan University Hospital, Taiwan
Background: Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3) is expressed in several malignancies, including melanomas. However, the expression of IMP-3 has not been explored in acral lentiginous melanoma (ALM). Objectives: Our purpose was to define the prognostic value of IMP-3 expression in ALMs.
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Methods: IMP-3 expression in 93 patients diagnosed with ALM was analyzed via immunohistochemistry. Univariate and multivariate analyses for survival, according to clinical and histologic tumor behaviors, were performed using the Cox proportional hazard model. Survival curves were plotted using the Kaplan–Meier method. Results: IMP-3 was expressed in 70 out of 93 tumors (75.3%). IMP-3 expression correlated with thick and high-stage tumor and predicted poorer overall, melanoma-specific, recurrence-free and distant metastasis-free survivals (P = 0.002, 0.006, 0.008 and 0.012, respectively). Further analysis showed that patients with tumor thickness ≤ 4.0 mm and positive IMP-3 expression had a significantly worse melanoma-specific survival than those without IMP-3 expression (P = 0.048). Multivariate survival analysis found that IMP-3 (hazard ratio 3.67, 95% confidence intervals 1.35–9.97, P = 0.011) proved to be an independent prognostic factor for melanoma-specific survival in ALMs. Conclusion: Positive IMP-3 expression correlates with thick and high-stage tumor and is an important prognostic factor of ALMs. http://dx.doi.org/10.1016/j.jdermsci.2016.08.528 P13-19[O2-50] Inhibition of melanogenesis by Gaillardia aristata flower extract Minkyung Kim Biospectrum Life Science Institute, Sangdaewon-Dong, Seongnam-City, Gyeonggi-Do, Republic of Korea The purpose of the study was to determine the anti-melanogenic and anti-oxidant properties of Gaillardia aristata flower extract (GAE). Melanogenesis inhibition by GAE was investigated in cultivated cells and in a human skin model. In cultivated cells, the melanogenesis regulatory effect of GAE was evaluated using melanin content, intracellular tyrosinase activity and anti-oxidant characteristics. In addition, the expression of melanogenesisrelated proteins was determined by Western blotting and real-time PCR. GAE reduced the amount of melanin in B16F 10 and normal human epidermal melanocyte cells and suppressed intracellular tyrosinase activity in a dose-dependent pattern. Also, GAE significantly decreased the expression of melanogenesis-related proteins (microphthalmia associated transcription factor, tyrosinase, tyrosinase- related protein-1, and dopachrome tautomerase). Real-time PCR results revealed a down-regulation of the mRNAs of these proteins. GAE possessed anti-oxidant characteristics as free radical-scavenging capacity and reducing power. In the threedimensional human skin model, GAE applied to hyperpigmented skin significantly increased the degree of skin lightening within 2 weeks of treatment. The safety of GAE on human skin was confirmed. The results indicate the potential of GAE for use in suppressing skin pigmentation. http://dx.doi.org/10.1016/j.jdermsci.2016.08.529
P13-17[O2-48] Hermansky–Pudlak syndrome type 4: The second case in Japanese Yuta Araki 1,∗ , Yoshiyuki Ishii 2 , Yuko Abe 1 , Junko Yoshizawa 1 , Fumiki Okamoto 3 , Yutaka Hozumi 1 , Tamio Suzuki 1 1
Department of Dermatology, Yamagata University School of Medicine, Yamagata, Japan 2 Department of Dermatology, Tsukuba University School of Medicine, Ibaraki, Japan 3 Department of Ophthalmology, Tsukuba University School of Medicine, Ibaraki, Japan Hermansky–Pudlak syndrome (HPS), a rare autosomal recessive disorder, is characterized by oculocutaneous albinism (OCA), bleeding tendency due to platelet storage pool deficiency and lysosomal accumulation of ceroid-lipofuscin. HPS4 is rare among Japanese people, and only one family with this form has been reported. We report a novel mutation in HPS4 in a HPS patient. This is the second reported case of HPS4 in a Japanese person. The patient was a 6-year-old Japanese girl with OCA. She had typical features such as white/pink skin with no apparent tanning ability, blond hair, light gray irides with nystagmus, and some purpura on her lower limbs. The purpura on her lower limbs had gradually increased, and her hair had recently turned from slightly yellow to blond. Fundoscopy showed hypopigmentation, translucent choroidal blood vessels and underdeveloped yellow spots, compared to the healthy control. The patient also had poor eyesight. Although there was no abnormality in the number of platelets or coagulation factors, her bleeding time was slightly prolonged (>5 min), suggesting a storage pool deficiency. We first screened the patient’s genomic DNA (extracted from peripheral blood) for mutations in the genes responsible for OCA1-4, and HPS1 that has been detected among Japanese people. However, no mutations were detected. We then screened the HPS3 and HPS4 genes by the polymerase chain reaction-single-strand conformation polymorphism and direct sequencing methods, because the patient showed a mild bleeding tendency. A novel homozygous mutation (c.730 C > T, p.Q244X) in exon 10 of the HPS4 gene was detected. There was no pathological mutation in the patient’s HPS3 gene. From these results, we diagnosed her as having HPS4. http://dx.doi.org/10.1016/j.jdermsci.2016.08.527 P13-18[O2-49] IMP-3 expression predicts unfavorable prognosis in acral lentiginous melanoma Yi-Shuan Sheen 1,2,∗ , Yi-Hua Liao 1 , Hsien-Ching Chiu 1 , Shiou-Hwa Jee 1 , Yih-Leong Chang 2 , Chia-Yu Chu 1 1 Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan 2 Graduate Institute of Pathology, College of Medicine, National Taiwan University and Department of Pathology, National Taiwan University Hospital, Taiwan
Background: Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3) is expressed in several malignancies, including melanomas. However, the expression of IMP-3 has not been explored in acral lentiginous melanoma (ALM). Objectives: Our purpose was to define the prognostic value of IMP-3 expression in ALMs.
e179
Methods: IMP-3 expression in 93 patients diagnosed with ALM was analyzed via immunohistochemistry. Univariate and multivariate analyses for survival, according to clinical and histologic tumor behaviors, were performed using the Cox proportional hazard model. Survival curves were plotted using the Kaplan–Meier method. Results: IMP-3 was expressed in 70 out of 93 tumors (75.3%). IMP-3 expression correlated with thick and high-stage tumor and predicted poorer overall, melanoma-specific, recurrence-free and distant metastasis-free survivals (P = 0.002, 0.006, 0.008 and 0.012, respectively). Further analysis showed that patients with tumor thickness ≤ 4.0 mm and positive IMP-3 expression had a significantly worse melanoma-specific survival than those without IMP-3 expression (P = 0.048). Multivariate survival analysis found that IMP-3 (hazard ratio 3.67, 95% confidence intervals 1.35–9.97, P = 0.011) proved to be an independent prognostic factor for melanoma-specific survival in ALMs. Conclusion: Positive IMP-3 expression correlates with thick and high-stage tumor and is an important prognostic factor of ALMs. http://dx.doi.org/10.1016/j.jdermsci.2016.08.528 P13-19[O2-50] Inhibition of melanogenesis by Gaillardia aristata flower extract Minkyung Kim Biospectrum Life Science Institute, Sangdaewon-Dong, Seongnam-City, Gyeonggi-Do, Republic of Korea The purpose of the study was to determine the anti-melanogenic and anti-oxidant properties of Gaillardia aristata flower extract (GAE). Melanogenesis inhibition by GAE was investigated in cultivated cells and in a human skin model. In cultivated cells, the melanogenesis regulatory effect of GAE was evaluated using melanin content, intracellular tyrosinase activity and anti-oxidant characteristics. In addition, the expression of melanogenesisrelated proteins was determined by Western blotting and real-time PCR. GAE reduced the amount of melanin in B16F 10 and normal human epidermal melanocyte cells and suppressed intracellular tyrosinase activity in a dose-dependent pattern. Also, GAE significantly decreased the expression of melanogenesis-related proteins (microphthalmia associated transcription factor, tyrosinase, tyrosinase- related protein-1, and dopachrome tautomerase). Real-time PCR results revealed a down-regulation of the mRNAs of these proteins. GAE possessed anti-oxidant characteristics as free radical-scavenging capacity and reducing power. In the threedimensional human skin model, GAE applied to hyperpigmented skin significantly increased the degree of skin lightening within 2 weeks of treatment. The safety of GAE on human skin was confirmed. The results indicate the potential of GAE for use in suppressing skin pigmentation. http://dx.doi.org/10.1016/j.jdermsci.2016.08.529