研究者詳細 - 武市　拓也

Paradoxical Reaction in a Patient with Hidradenitis Suppurativa Undergoing Adalimumab Treatment. 査読有り国際誌

Ikeya S, Takeichi T, Taki T, Muro Y, Ogi T, Akiyama M

Acta dermato-venereologica 101 巻 ( 6 ) 頁： adv00484 2021年6月

Establishment of in-hospital clinical network for patients with neurofibromatosis type 1 in Nagoya University Hospital 査読有り国際誌

Nishida, Y; Ikuta, K; Natsume, A; Ishihara, N; Morikawa, M; Kidokoro, H; Muramatsu, Y; Nonobe, N; Ishizuka, K; Takeichi, T; Kanbe, M; Mizuno, S; Imagama, S; Ozaki, N

SCIENTIFIC REPORTS 11 巻 ( 1 ) 頁： 11933 - 11933 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Scientific Reports

Neurofibromatosis type 1 (NF1) is a genetic multisystem disorder. Clinicians must be aware of the diverse clinical features of this disorder in order to provide optimal care for it. We have set up an NF1 in-hospital medical care network of specialists regardless of patient age, launching a multidisciplinary approach to the disease for the first time in Japan. From January 2014 to December 2020, 246 patients were enrolled in the NF1 patient list and medical records. Mean age was 26.0 years ranging from 3 months to 80 years. The number of patients was higher as age at first visit was lower. There were 107 males (41%) and 139 females. After 2011, the number of patients has increased since the year when the medical care network was started. Regarding orthopedic signs, scoliosis was present in 60 cases (26%), and bone abnormalities in the upper arm, forearm, and tibia in 8 cases (3.5%). Neurofibromas other than cutaneous neurofibromas were present in 90 cases (39%), and MPNST in 17 cases (7.4%). We launched a multidisciplinary NF1 clinic system for the first time in Japan. For patients with NF1, which is a hereditary and systemic disease associated with a high incidence of malignant tumors, it will be of great benefit when the number of such clinics in Japan and the rest of Asia is increased.

DOI： 10.1038/s41598-021-91345-6

Altered replication stress response due to CARD14 mutations promotes recombination-induced revertant mosaicism 査読有り国際誌

Miyauchi, T; Suzuki, S; Takeda, M; Peh, JT; Aiba, M; Natsuga, K; Fujita, Y; Takeichi, T; Sakamoto, T; Akiyama, M; Shimizu, H; Nomura, T

AMERICAN JOURNAL OF HUMAN GENETICS 108 巻 ( 6 ) 頁： 1026 - 1039 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Journal of Human Genetics

Revertant mosaicism, or “natural gene therapy,” refers to the spontaneous in vivo reversion of an inherited mutation in a somatic cell. Only approximately 50 human genetic disorders exhibit revertant mosaicism, implicating a distinctive role played by mutant proteins in somatic correction of a pathogenic germline mutation. However, the process by which mutant proteins induce somatic genetic reversion in these diseases remains unknown. Here we show that heterozygous pathogenic CARD14 mutations causing autoinflammatory skin diseases, including psoriasis and pityriasis rubra pilaris, are repaired mainly via homologous recombination. Rather than altering the DNA damage response to exogenous stimuli, such as X-irradiation or etoposide treatment, mutant CARD14 increased DNA double-strand breaks under conditions of replication stress. Furthermore, mutant CARD14 suppressed new origin firings without promoting crossover events in the replication stress state. Together, these results suggest that mutant CARD14 alters the replication stress response and preferentially drives break-induced replication (BIR), which is generally suppressed in eukaryotes. Our results highlight the involvement of BIR in reversion events, thus revealing a previously undescribed role of BIR that could potentially be exploited to develop therapeutics for currently intractable genetic diseases.

DOI： 10.1016/j.ajhg.2021.04.021

Hereditary Mucoepithelial Dysplasia and Autosomal-Dominant IFAP Syndrome Is a Clinical Spectrum Due to SREBF1 Variants 査読有り国際誌

Murase, C; Takeichi, T; Nomura, T; Ogi, T; Akiyama, M

JOURNAL OF INVESTIGATIVE DERMATOLOGY 141 巻 ( 6 ) 頁： 1596 - 1598 2021年6月

Autoantibody profiles in patients' sera associated with distribution patterns of dermatomyositis skin symptoms 査読有り国際誌

Ogawa-Momohara, M; Kinoshita, F; Muro, Y; Kobayashi, Y; Takeichi, T; Akiyama, M

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY 84 巻 ( 6 ) 頁： 1720 - + 2021年6月

MEDNIK-like syndrome due to compound heterozygous mutations in AP1B1 査読有り

Ito, Y; Takeichi, T; Igari, S; Mori, T; Ono, A; Suyama, K; Takeuchi, S; Muro, Y; Ogi, T; Hosoya, M; Yamamoto, T; Akiyama, M

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY 35 巻 ( 5 ) 頁： E345 - E347 2021年5月

Successful dupilumab treatment for ichthyotic and atopic features of Netherton syndrome 査読有り国際誌

Murase, C; Takeichi, T; Taki, T; Yoshikawa, T; Suzuki, A; Ogi, T; Suga, Y; Akiyama, M

JOURNAL OF DERMATOLOGICAL SCIENCE 102 巻 ( 2 ) 頁： 126 - 129 2021年5月

Odontogenic keratocysts are an important clue for diagnosing basal cell nevus syndrome 査読有り

Kaibuchi-Ando, K; Takeichi, T; Ito, Y; Takeuchi, S; Yamashita, Y; Yamada, M; Muro, Y; Ogi, T; Akiyama, M

NAGOYA JOURNAL OF MEDICAL SCIENCE 83 巻 ( 2 ) 頁： 393 - 396 2021年5月

記述言語：英語出版者・発行元：Nagoya Journal of Medical Science

Basal cell nevus syndrome (BCNS) is an autosomal dominant skin disorder characterized by multiple basal cell nevi. Patients with BCNS tend to develop basal cell carcinoma (BCC) and frequently show skeletal abnormalities. Most cases of BCNS are caused by mutations in patched 1 (PTCH1). PTCH1 encodes a transmembrane receptor protein for the secreted molecule sonic hedgehog, which plays a key role in the development of animals ranging from insects to mammals. We analyzed two Japanese BCNS patients from two independent families. Both of our patients had multiple jaw keratocysts. In one patient, these were the key to noticing his BCNS, as he had no skin tumors. The early detection of PTCH1 mutations would enable BCNS patients to be carefully followed up for the occurrence of BCC. The diagnosis of BCC at the early stage leads to prompt surgical treatments, resulting in a good prognosis. The present cases suggest that keratocysts of the jaw might be an important clue for diagnosing BCNS.

DOI： 10.18999/nagjms.83.2.393