Details of a Researcher - Amagai, Masayuki

Papers - Amagai, Masayuki

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Early symptoms preceding post-infectious irritable bowel syndrome following COVID-19: a retrospective observational study incorporating daily gastrointestinal symptoms

Yamamoto R., Yamamoto A., Masaoka T., Homma K., Matsuoka T., Takemura R., Wada M., Sasaki J., Kanai T., Amagai M., Saya H., Nishihara H.

BMC Gastroenterology (BMC Gastroenterology) 23 ( 1 ) 2023.12

Background: Intestinal microinflammation with immune dysfunction due to severe acute respiratory syndrome coronavirus 2 reportedly precipitates post-infectious irritable bowel syndrome. This study aimed to elucidate potential risk factors for subsequent development of irritable bowel syndrome, hypothesizing that it is associated with specific symptoms or patient backgrounds. Methods: This single-center retrospective observational study (2020–2021) included adults with confirmed coronavirus disease requiring hospital admission and was conducted using real-world data retrieved from a hospital information system. Patient characteristics and detailed gastrointestinal symptoms were obtained and compared between patients with and without coronavirus disease-induced irritable bowel syndrome. Multivariate logistic models were used to validate the risk of developing irritable bowel syndrome. Moreover, daily gastrointestinal symptoms during hospitalization were examined in patients with irritable bowel syndrome. Results: Among the 571 eligible patients, 12 (2.1%) were diagnosed with irritable bowel syndrome following coronavirus disease. While nausea and diarrhea during hospitalization, elevated white blood cell count on admission, and intensive care unit admission were associated with the development of irritable bowel syndrome, nausea and diarrhea were identified as risk factors for its development following coronavirus disease, as revealed by the adjusted analyses (odds ratio, 4.00 [1.01–15.84] and 5.64 [1.21–26.31], respectively). Half of the patients with irritable bowel syndrome had both diarrhea and constipation until discharge, and constipation was frequently followed by diarrhea. Conclusions: While irritable bowel syndrome was rarely diagnosed following coronavirus disease, nausea and diarrhea during hospitalization precede the early signs of irritable bowel syndrome following coronavirus disease.

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Dissecting skin microbiota and microenvironment for the development of therapeutic strategies

Ito Y., Amagai M.

Current Opinion in Microbiology (Current Opinion in Microbiology) 74 2023.08

ISSN 13695274

The skin is a pivotal barrier between the human body and the environment, and is a habitat for numerous microorganisms. While host–microbiota interactions in the skin are essential for homeostasis, disturbances in microbial composition and the abnormal growth of certain bacteria are associated with various diseases. Here, we identify strains and communities of skin commensals that contribute to or impair skin barrier function. Furthermore, we discuss the skin microenvironments suitable for specific microbiota that exert therapeutic effects and suggest focus areas for the prospective development of therapeutic strategies using bacterial agents. Finally, we highlight recent efforts to treat skin diseases associated with live bacteria.

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Diverse Role of OX40 on T Cells as a Therapeutic Target for Skin Diseases

Iriki H., Takahashi H., Amagai M.

Journal of Investigative Dermatology (Journal of Investigative Dermatology) 143 ( 4 ) 545 - 553 2023.04

ISSN 0022202X

OX40 is an important costimulatory molecule for T-cell expansion and survival. Because OX40 is expressed on most T-cell subsets, it is an attractive therapeutic target for a variety of T-cell‒mediated diseases. Clinical trials are already underway for some skin inflammatory diseases. In this review, we present various observations that improve our understanding of how OX40-targeted therapy can be applied for skin inflammatory diseases, such as atopic dermatitis and psoriasis, T helper (Th)2- and Th17-mediated diseases, respectively. The important OX40/OX40L-mediated interaction between T cells and other immune cells is also discussed in terms of skin autoimmune diseases, such as alopecia areata and pemphigus. Regulatory T cells (Tregs) highly express OX40, and the skin harbors a large Treg population; thus, understanding how OX40-targeted treatment acts on Tregs is vital for the development of therapeutic strategies for various skin diseases.

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Clinical severity scores as a guide for prediction of initial treatment responses in pemphigus and pemphigoid patients

Tanaka R., Kurihara Y., Egami S., Saito Y., Ouchi T., Funakoshi T., Takahashi H., Umegaki-Arao N., Kubo A., Tanikawa A., Amagai M., Yamagami J.

Journal of Dermatology (Journal of Dermatology) 50 ( 2 ) 203 - 211 2023.02

ISSN 03852407

Pemphigus and pemphigoid are autoimmune blistering diseases that affect mucosa and skin. Several clinical scoring systems, including the pemphigus disease area index (PDAI) and the bullous pemphigoid disease area index (BPDAI), have been validated for managing disease activity and severity. Current guidelines recommend that treatment response be evaluated with clinical scores and that additional second-line therapies be considered if initial treatment is insufficient for disease control. However, there have been few studies analyzing correlations between PDAI/BPDAI transitions and initial treatment effects. To investigate whether PDAI/BPDAI transitions during the treatment initiation phase correlate with initial treatment responses and whether such information can be used as a guide for necessary additional treatment, we retrospectively analyzed 67 pemphigus patients and 47 pemphigoid patients who received initial treatment at Keio University between 2012 and 2018. The clinical symptoms were evaluated weekly with PDAI/BPDAI. The patients were divided into two groups: in group A, disease was controlled only with oral corticosteroids and immunosuppressants (initial treatment), whereas in group B additional therapies were required due to insufficient responses. In pemphigus, the PDAI ratio of day 7/day 0 was significantly reduced in group A compared to group B (0.548 vs 0.761, P < 0.01) after initial treatment had started. In pemphigoid, the ratios of day 7/day 0 of BPDAI (erosion/blister) and BPDAI (urticaria/erythema) significantly decreased in group A compared to group B (0.565 vs 0.901 and 0.350 vs 0.760, respectively, P < 0.05). Receiver operating characteristic analyses on PDAI, BPDAI (erosion/blister) and BPDAI (urticaria/erythema) revealed that the cut-off values in the ratios of day 7/day 0 were 0.762, 0.675, and 0.568, respectively. Our results suggest that PDAI/BPDAI transitions during the initial phase of the treatments may be useful to predict the outcome of the treatment provided and the necessity of additional therapies to achieve disease control.

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Rituximab therapy for intractable pemphigus: A multicenter, open-label, single-arm, prospective study of 20 Japanese patients

Yamagami J., Kurihara Y., Funakoshi T., Saito Y., Tanaka R., Takahashi H., Ujiie H., Iwata H., Hirai Y., Iwatsuki K., Ishii N., Sakurai J., Abe T., Takemura R., Mashino N., Abe M., Amagai M.

Journal of Dermatology (Journal of Dermatology) 50 ( 2 ) 175 - 182 2023.02

ISSN 03852407

This was a multicenter clinical trial of rituximab, a chimeric monoclonal IgG antibody directed against CD20, for the treatment of refractory pemphigus vulgaris and pemphigus foliaceus. In total, 20 patients were treated with two doses of rituximab (1000 mg; 2 weeks apart) on days 0 and 14. The primary end point was the proportion of patients who achieved complete or partial remission on day 168 following the first rituximab dose. Of the 20 enrolled patients, 11 (55%) and four (20%) achieved complete and partial remission, respectively; therefore, remission was achieved in a total of 15 patients (75.0% [95% confidence interval, 50.9%–91.3%]). It was demonstrated that the remission rate was greater than the prespecified threshold (5%). In addition, a significant improvement in clinical score (Pemphigus Disease Area Index) and decrease in serum anti-desmoglein antibody level were observed over time. Four serious adverse events (heart failure, pneumonia, radial fracture, and osteonecrosis) were recorded in two patients, of which only pneumonia was considered causally related with rituximab. The level of peripheral blood CD19-positive B lymphocytes was decreased on day 28 after rituximab treatment and remained low throughout the study period until day 168. Our results confirm the efficacy and safety of rituximab therapy for refractory pemphigus in Japanese patients.

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Two sporadic cases of childhood-onset Hailey-Hailey disease with superimposed mosaicism

Asahina Y., Tahara U., Aoki S., Nakabayashi K., Tateishi C., Hayashi D., Amagai M., Tsuruta D., Kubo A.

European Journal of Human Genetics (European Journal of Human Genetics) 2023

ISSN 10184813

A prenatal second-hit genetic change that occurs on the wild-type allele in an embryo with a congenital pathogenic variant allele results in mosaicism of monoallelic and biallelic defect of the gene, which is called superimposed mosaicism. Superimposed mosaicism of Hailey-Hailey disease (HHD) has been demonstrated in one familial case. Here, we report two unrelated HHD cases with superimposed mosaicism: a congenital monoallelic pathogenic variant of ATP2C1, followed by a postzygotic copy-neutral loss of heterozygosity. Uniquely, neither patient had a family history of HHD at the time of presentation. In the first case, the congenital pathogenic variant had occurred de novo. In the second case, the father had the pathogenic variant but had not yet developed skin symptoms. Our cases showed that superimposed mosaicism in HHD can lack a family history and that genetic analysis is crucial to classify the type of mosaicism and evaluate the risk of familial occurrence.

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Desmoglein-Specific B-Cell−Targeted Single-Cell Analysis Revealing Unique Gene Regulation in Patients with Pemphigus

Egami S., Watanabe T., Fukushima-Nomura A., Nomura H., Takahashi H., Yamagami J., Ohara O., Amagai M.

Journal of Investigative Dermatology (Journal of Investigative Dermatology) 2023

ISSN 0022202X

Autoreactive B cells are assumed to play a critical role in pemphigus; however, the characteristics of these cells are not yet fully understood. In this study, 23 pemphigus vulgaris or pemphigus foliaceus samples were used to isolate circulating desmoglein (DSG)-specific B cells. Transcriptome analysis of the samples was performed at the single-cell level to detect genes involved in disease activity. DSG1- or DSG3-specific B cells from three patients’ differentially expressed genes related to T cell costimulation (CD137L) as well as B-cell differentiation (CD9, BATF, TIMP1) and inflammation (S100A8, S100A9, CCR3), compared with nonspecific B cells from the same patients. When the DSG1-specific B cells before and after treatment transcriptomes of the patient with pemphigus foliaceus were compared, there were changes in several B-cell activation pathways not detected in non−DSG1-specific B cells. This study clarifies the transcriptomic profile of autoreactive B cells in patients with pemphigus and documents the gene expression related to disease activity. Our approach can be applied to other autoimmune diseases and has the potential for future detection of disease-specific autoimmune cells.

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Controlling skin microbiome as a new bacteriotherapy for inflammatory skin diseases

Ito Y., Amagai M.

Inflammation and Regeneration (Inflammation and Regeneration) 42 ( 1 ) 2022.12

The skin serves as the interface between the human body and the environment and interacts with the microbial community. The skin microbiota consists of microorganisms, such as bacteria, fungi, mites, and viruses, and they fluctuate depending on the microenvironment defined by anatomical location and physiological function. The balance of interactions between the host and microbiota plays a pivotal role in the orchestration of skin homeostasis; however, the disturbance of the balance due to an alteration in the microbial communities, namely, dysbiosis, leads to various skin disorders. Recent developments in sequencing technology have provided new insights into the structure and function of skin microbial communities. Based on high-throughput sequencing analysis, a growing body of evidence indicates that a new treatment using live bacteria, termed bacteriotherapy, is a feasible therapeutic option for cutaneous diseases caused by dysbiosis. In particular, the administration of specific bacterial strains has been investigated as an exclusionary treatment strategy against pathogens associated with chronic skin disorders, whereas the safety, efficacy, and sustainability of this therapeutic approach using isolated live bacteria need to be further explored. In this review, we summarize our current understanding of the skin microbiota, as well as therapeutic strategies using characterized strains of live bacteria for skin inflammatory diseases. The ecosystem formed by interactions between the host and skin microbial consortium is still largely unexplored; however, advances in our understanding of the function of the skin microbiota at the strain level will lead to the development of new therapeutic methods.

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Pro108Ser mutation of SARS-CoV-2 3CL<sup>pro</sup> reduces the enzyme activity and ameliorates the clinical severity of COVID-19

Abe K., Kabe Y., Uchiyama S., Iwasaki Y.W., Ishizu H., Uwamino Y., Takenouchi T., Uno S., Ishii M., Maruno T., Noda M., Murata M., Hasegawa N., Saya H., Kitagawa Y., Fukunaga K., Amagai M., Siomi H., Suematsu M., Kosaki K.

Scientific Reports (Scientific Reports) 12 ( 1 ) 2022.12

Recently, an international randomized controlled clinical trial showed that patients with SARS-CoV-2 infection treated orally with the 3-chymotrypsin-like protease (3CLpro) inhibitor PF-07321332 within three days of symptom onset showed an 89% lower risk of COVID-19-related hospital admission/ death from any cause as compared with the patients who received placebo. Lending support to this critically important result of the aforementioned trial, we demonstrated in our study that patients infected with a SARS-Cov-2 sub-lineage (B.1.1.284) carrying the Pro108Ser mutation in 3CLpro tended to have a comparatively milder clinical course (i.e., a smaller proportion of patients required oxygen supplementation during the clinical course) than patients infected with the same sub-lineage of virus not carrying the mutation. Characterization of the mutant 3CLpro revealed that the Kcat/Km of the 3CLpro enzyme containing Ser108 was 58% lower than that of Pro108 3CLpro. Hydrogen/deuterium-exchange mass spectrometry (HDX-MS) revealed that the reduced activity was associated with structural perturbation surrounding the substrate-binding region of the enzyme, which is positioned behind and distant from the 108th amino acid residue. Our findings of the attenuated clinical course of COVID-19 in patients infected with SARS-CoV-2 strains with reduced 3CLpro enzymatic activity greatly endorses the promising result of the aforementioned clinical trial of the 3CLpro inhibitor.

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Microbiota-Independent Spontaneous Dermatitis Associated with Increased Sebaceous Lipid Production in Tmem79-Deficient Mice

Morimoto A., Fukuda K., Ito Y., Tahara U., Sasaki T., Shiohama A., Kawasaki H., Kawakami E., Naganuma T., Arita M., Sasaki H., Koseki H., Matsui T., Amagai M.

Journal of Investigative Dermatology (Journal of Investigative Dermatology) 142 ( 11 ) 2864 - 2872.e6 2022.11

ISSN 0022202X

TMEM79 is a predisposing gene for atopic dermatitis. Tmem79-deficient mice develop spontaneous dermatitis in a biphasic pattern. The first-phase dermatitis is unique because it occurs independent of microbiota status, whereas the second-phase dermatitis is microbiota dependent. In this study, we sought to identify the key factors mediating the development of first-phase dermatitis. Structural analysis showed that sebaceous gland hyperplasia started from first-phase dermatitis. Longitudinal RNA sequencing analysis revealed significant activation of fatty acid lipid metabolism pathways in first-phase dermatitis, whereas T helper 17‒based immune response genes were highly expressed in second-phase dermatitis. Quantitative RT-PCR analysis revealed that genes involved in fatty acid elongation and sebocyte differentiation were upregulated in first-phase dermatitis. The results of thin-layer chromatography supported these findings with an increased abundance of wax esters, cholesterol esters, and fatty alcohols in hair lipids. Further gas chromatography-tandem mass spectrometry analysis showed an increase in total fatty acid production, including that of elongated C20–24 saturated and C18–24 monounsaturated fatty acids. Collectively, these results suggest that aberrant production of sebaceous long-chain fatty acids is associated with microbiota-independent dermatitis. Further investigation of Tmem79-deficient mice may clarify the role of certain fatty acids in dermatitis.

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Neurofibromatosis type 2 with mild Pierre-Robin sequence showing a heterozygous chromosome 22q12 microdeletion encompassing NF2 and MN1

Saito S., Ono N., Sasaki T., Aoki S., Kosaki K., Kuze B., Nakabayashi K., Amagai M., Kubo A.

Journal of Human Genetics (Journal of Human Genetics) 67 ( 11 ) 675 - 678 2022.11

ISSN 14345161

Pierre-Robin sequence (PRS) is a rare, congenital defect presenting with micrognathia, glossoptosis, and airway obstruction with variable inclusion of a cleft palate. Overlapping PRS with neurofibromatosis type 2 (NF2) is a syndrome caused by a chromosome 22q12 microdeletion including NF2. We describe a patient with severe early-onset NF2 overlapping with PRS that showed micrognathia, glossoptosis, and a mild form of cleft palate. We detected a de novo chromosome 22q12 microdeletion including MN1 and NF2 in the patient. Previous cases of overlapping PRS and NF2 caused by the chromosome 22q12 microdeletions showed severe NF2 phenotypes with variable severity of cleft palate and microdeletions of varying sizes. Genotype-phenotype correlations and comparison of the size and breakpoint of microdeletions suggest that some modifier genes distal to MN1 and NF2 might be linked to the cleft palate severity.

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Severe graft-versus-host disease-like enterocolitis accompanied with cytomegalovirus-reactivation in drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms

Takamiyagi S., Iriki H., Asahina Y., Furuichi Y., Funakoshi T., Ichikawa M., Mikami Y., Okita H., Sakiyama T., Inazumi T., Amagai M., Takahashi H.

Journal of Dermatology (Journal of Dermatology) 49 ( 8 ) 796 - 799 2022.08

ISSN 03852407

Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug adverse reaction with skin eruption and visceral organ involvement. The characteristic clinical features of DIHS/DRESS are reactivation of human herpesviruses (HHV) and the development of autoimmune diseases, but their pathogenesis and associations are not yet understood. Here, we report a 66-year-old man who presented with fever, generalized erythema, diffuse lymphadenopathy, and diarrhea after 3 weeks of treatment with zonisamide. Reactivation of HHV-6 and cytomegalovirus (CMV) was detected during the clinical course. The patient was diagnosed with DIHS/DRESS and treated with systemic prednisolone, i.v. immunoglobulin therapy, and ganciclovir. However, severe enterocolitis persisted for 6 months. A series of examinations revealed features of both CMV enterocolitis, as indicated by identification of a few CMV-positive cells on immunohistochemical analysis, and graft-versus-host disease (GVHD)-like enterocolitis indicated by orange-peel appearance on endoscopic examination and histopathological loss of goblet cells. Intractable enterocolitis continued and the patient finally died of pneumonia. An autoimmune predisposition in DIHS/DRESS patients in combination with CMV reactivation was considered to trigger the severe enterocolitis of this case that showed GVHD-like features of the gastrointestinal tract. GVHD-like organ damage is a pathological condition rarely observed in DIHS/DRESS but should be recognized as one of the most severe complications of the disease.

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Intravenous Ig Regulates Anti-Desmoglein 3 IgG Production in B220<sup>–</sup> Antibody-Producing Cells in Mice with Pemphigus Vulgaris

Kase Y., Takahashi H., Ito H., Kamata A., Amagai M., Yamagami J.

Journal of Investigative Dermatology (Journal of Investigative Dermatology) 142 ( 7 ) 1786 - 1792.e3 2022.07

ISSN 0022202X

Intravenous Ig (IVIG) is a treatment option for intractable cases of pemphigus vulgaris (PV), an autoimmune blistering disease caused by autoantibodies against desmoglein 3 (DSG3). To investigate the efficacy of IVIG on autoantibody secretion, we produced PV model mice by adoptive transfer of immunized Dsg3−/− splenocytes to Rag2−/− mice. We found that circulating anti-DSG3 IgG ELISA titer decreased in PV model mice after 5 days of treatment with IVIG compared with PBS-treated mice, whereas the F(ab’)2 fragment did not suppress the anti-DSG3 IgG titer. enzyme-linked immunospot assay revealed that IVIG treatment reduced the frequency of anti-DSG3 antibody–secreting cells in the spleen but not in lymph nodes and bone marrow. Moreover, this reduction was observed only in the splenic B220− fraction but not in the B220+ fraction. Furthermore, IVIG decreased the serum levels of anti-DSG3 IgG, even after a significant reduction of its titer, owing to antibody-mediated CD20+ B cell depletion. In addition, IVIG suppressed anti-DSG3 IgG production in B220−CD138+ plasma cells derived from PV model mice ex vivo. These results indicate that IVIG reduced autoantibody production in B220− cells containing plasma cells in PV model mice, and this function may indicate one of the mechanisms of action of IVIG on PV.

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Superimposition of checkerboard distribution of ephelides and neurofibromas in a patient with segmental neurofibromatosis

Iriki H., Umegaki-Arao N., Kakuta R., Fujita H., Aoki S., Amagai M., Sasaki T., Hamamoto Y., Nakayama R., Kubo A.

JAAD Case Reports (JAAD Case Reports) 25 89 - 92 2022.07

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【手足の皮膚病】関節リウマチの症状増悪に伴い出現したBywaters' lesions

田村佳奈, 角田梨沙, 金子祐子, 天谷雅行, 谷川瑛子

皮膚病診療 ((株)協和企画) 44 ( 7 ) 604 - 607 2022.07

ISSN 0387-7531

＜文献概要＞症例のポイント　・各種治療に抵抗性の30年来の関節リウマチの患者に,手指爪囲の紫斑や血疱が出現し,病理組織像で真皮小血管の閉塞像が確認されたことからBywaters' lesions(BL)と診断した.・治療経過中,関節リウマチの血清抗体価上昇および関節症状・関節外症状の出現など関節リウマチが増悪するたびにBLが出現する傾向がみられた.・関節リウマチ患者においてBLを認めた際には,病勢増悪や血管炎を疑わせる症状の有無に注意して,慎重に経過を追うことが大切である.

Highly Precise, Continuous, Long-Term Monitoring of Skin Electrical Resistance by Nanomesh Electrodes

Miyamoto A., Kawasaki H., Lee S., Yokota T., Amagai M., Someya T.

Advanced Healthcare Materials (Advanced Healthcare Materials) 11 ( 10 ) 2022.05

ISSN 21922640

The transepidermal water loss has been widely used as a method for directly evaluating the barrier function of the stratum corneum of the skin. However, transepidermal water loss could not be measured continuously for a long period of time, and there were no reports of continuous monitoring of skin barrier functions. Here, a method is reported to continuously monitor the skin electrical resistance by nanomesh electrodes for a long period of time while maintaining the natural skin condition that does not inhibit water evaporation. Simultaneous measurements of the skin electrical resistance by nanomesh electrodes and transepidermal water loss exhibits a linear fit with a high negative correlation. Furthermore, dynamics of skin physiological functions are successfully visualized by monitoring of the skin electrical resistance by nanomesh electrodes for 30 h in daily life.

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Increase in the Intracellular Bulk Water Content in the Early Phase of Cell Death of Keratinocytes, Corneoptosis, as Revealed by 65 GHz Near-Field CMOS Dielectric Sensor

Shiraga K., Ogawa Y., Kikuchi S., Amagai M., Matsui T.

Molecules (Molecules) 27 ( 9 ) 2022.05

While bulk water and hydration water coexist in cells to support the expression of biological macromolecules, how the dynamics of water molecules, which have long been only a minor role in molecular biology research, relate to changes in cellular states such as cell death has hardly been explored so far due to the lack of evaluation techniques. In this study, we developed a high-preci-sion measurement system that can discriminate bulk water content changes of ±0.02% (0.2 mg/cm3) with single-cell-level spatial resolution based on a near-field CMOS dielectric sensor operating at 65 GHz. We applied this system to evaluate the temporal changes in the bulk water content during the cell death process of keratinocytes, called corneoptosis, using isolated SG1 (first layer of stratum granulosum) cells in vitro. A significant irreversible increase in the bulk water content was observed approximately 1 h before membrane disruption during corneoptosis, which starts with cytoplasmic high Ca2+ signal. These findings suggest that the calcium flux may have a role in triggering the increase in the bulk water content in SG1 cells. Thus, our near-field CMOS dielectric sensor provides a valuable tool to dissect the involvement of water molecules in the various events that occur in the cell.

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【(新規)抗腫瘍薬〜光と影〜】ドセタキセル・ゲムシタビン併用療法と放射線治療が奏効した頭部血管肉腫

鎌田亜紀, 平井郁子, 中村善雄, 齋藤昌孝, 天谷雅行, 舩越建

皮膚病診療 ((株)協和企画) 44 ( 5 ) 406 - 409 2022.05

ISSN 0387-7531

【遺伝性疾患と遺伝カウンセリング】NCSTN遺伝子変異を同定した家族性化膿性汗腺炎/familial acne inversaの姉妹例

小野紀子, 田中諒, 中林一彦, 秦健一郎, 鈴木寿人, 小崎健次郎, 天谷雅行, 久保亮治

皮膚病診療 ((株)協和企画) 44 ( 3 ) 215 - 219 2022.03

ISSN 0387-7531

＜文献概要＞症例のポイント　・53歳女.高校生ごろからざ瘡が多発し,頸部から体幹,四肢にかけて大小の嚢胞性皮下腫瘤が散在.腋窩・鼠径部に瘻孔を形成,排膿を繰り返していた.・本人および妹に家族性化膿性汗腺炎/familial acne inversaの病原性変異として報告されているNCSTNのナンセンス変異を同定した.・家族性化膿性汗腺炎/familial acne inversaは常染色体優性遺伝のため,次世代に遺伝する確率は50%である.妹には未成年の子どもが3人いるが,未発症未成年の遺伝学的検査は本人が成人してから本人の意思で施行するのが原則である.

【遺伝性疾患と遺伝カウンセリング】母子間で皮疹の分布範囲が大きく異なったGoltz症候群

田原海, 小野紀子, 青木里美, 天谷雅行, 久保亮治

皮膚病診療 ((株)協和企画) 44 ( 3 ) 232 - 235 2022.03

ISSN 0387-7531

＜文献概要＞症例のポイント　・PORCNの片アレル欠失によって発症した,Goltz症候群の母子例を報告した.母は生下時から両側の広大な範囲に皮疹を認めた一方で,娘は片側のごく限られた範囲にのみ皮疹を認めた.・母子間でGoltz症候群の皮疹の分布範囲が大きく異なった原因として,ランダムにおこったX染色体不活化の結果,皮膚組織において正常なPORCNを発現せず病変部をつくる細胞の割合に差があったと考えられた.PORCNに遺伝学的変化を有する場合でも,皮疹の範囲は発生初期におこるX染色体不活化の結果をそのまま反映することが示唆され,次子が同疾患に罹患した場合は姉妹間でも皮疹の範囲が大きく異なる可能性があることを両親に伝えた.

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