Research activity information

• Oct. 2023 The 22nd Congress of the Federation of Asia and Oceania Perinatal Societies, Best Congress Awards, Influence of genetic variants on unbound bilirubin levels in Japanese newborns: a preliminary study

  Hiroaki Hanafusa


• May 2023 第65回日本小児神経学会学術集会 若手優秀演題賞 一般口演

  Japan society

• Total Intramuscular Fat Fraction of Thigh Muscles as a Predictor of Nusinersen Efficacy in Pediatric SMA Type II and III

  Kiiko Iketani, Hiroyuki Awano, Hiromi Hashimura, Shoko Sonehara, Hiroaki Hanafusa, Yoshinori Nambu, Hisahide Nishio, Kandai Nozu, Ryosuke Bo

  Mar. 2025, Diagnostics

  Scientific journal


• Epidemiology of SARS-CoV-2 Infection in Patients with Neuromuscular Disease and Inborn Errors of Metabolism: A Cross-sectional Study for a Pediatric Outpatient Referral in Japan.

  Sungwon Hong, Kiiko Iketani, Shoko Sonehara, Hiroaki Hanafusa, Yoshinori Nambu, Kandai Nozu, Hiroyuki Awano, Ryosuke Bo

  The coronavirus disease 2019 (COVID-19) pandemic has affected people worldwide, and pediatric patients with underlying diseases are at high risk of developing severe COVID-19. However, there are limited reports on the clinical impact of COVID-19, especially in patients with underlying neuromuscular diseases (NMD) and inborn errors of metabolism (IEM). This study aimed to investigate the incidence and clinical presentation of COVID-19 in patients with NMD and IEM. This was a single-center, cross-sectional study of patients with NMD and IEM in Japan for 2 years, from April 1, 2020 to March 31, 2022. Among 255 participants with a median age of 14 (range: 0-50) years, 192 (75%) and 63 (25%) had NMD and IEM, respectively. Among 255 patients, 8 (5 NMD and 3 IEM) were positive for the anti-severe acute respiratory syndrome coronavirus 2 nucleocapsid antibody, and the incidence was considered 3%. All positive patients had mild or asymptomatic COVID-19. None of the patients exhibited moderate or severe symptoms. In conclusion, this study revealed that the incidence of COVID-19 was low, and mild or subclinical infection was common even in patients with NMD and IEM, who may be at a higher risk of severe COVID-19.

  Feb. 2025, The Kobe journal of medical sciences, 70(4) (4), E106-E112, English, Domestic magazine

  Scientific journal


• 兵庫県/神戸市の拡大新生児マススクリーニングにおけるポンペ病精密検査例の遺伝学的背景と酵素活性の検討

  曽根原 晶子, 大橋 浩基, 松井 美樹, 花房 宏昭, 南部 静紀, 李 知子, 粟野 宏之, 竹島 泰弘, 野津 寛大, 坊 亮輔

  (一社)日本マススクリーニング学会, Jul. 2024, 日本マス・スクリーニング学会誌, 34(2) (2), 209 - 209, Japanese


• 3歳時の朝食習慣と小学1年生での学力との関連 尼崎市の人口ベースコホート研究

  川村 葵, 西山 将広, 伊藤 立人, 京野 由紀, 鮫島 智大, 花房 宏昭, 老川 静香, 徳元 翔一, 山口 宏, 野津 寛大, 永瀬 裕朗

  (一社)日本小児神経学会, May 2024, 脳と発達, 56(Suppl.) (Suppl.), S206 - S206, Japanese


• End-stage ADPKD with a low-frequency PKD1 mosaic variant accelerated by chemoradiotherapy.

  Hiroaki Hanafusa, Hiroshi Yamaguchi, Naoya Morisada, Ming Juan Ye, Riki Matsumoto, Hiroaki Nagase, Kandai Nozu

  Autosomal dominant polycystic kidney disease (ADPKD) is commonly caused by PKD1, and mosaic PKD1 variants result in milder phenotypes. We present the case of a 32 year-old male with chronic active Epstein-Barr virus who underwent bone marrow transplantation with chemoradiotherapy at age 9. Despite a low-frequency mosaic splicing PKD1 variant, he developed severe renal cysts and end-stage renal disease in his 30 s. This case highlights how environmental factors may contribute to the genetic predisposition to ADPKD.

  Mar. 2024, Human genome variation, 11(1) (1), 17 - 17, English, International magazine

  Scientific journal


• A novel NFKB1 variant in a Japanese pedigree with common variable immunodeficiency.

  Naoko Nakatani, Akihiro Tamura, Hiroaki Hanafusa, Nanako Nino, Nobuyuki Yamamoto, Hiroyuki Awano, Yasuhiro Tanaka, Naoya Morisada, Suguru Uemura, Atsuro Saito, Daiichiro Hasegawa, Kandai Nozu, Yoshiyuki Kosaka

  Recently, heterozygous loss-of-function NFKB1 variants were identified as the primary cause of common variable immunodeficiency (CVID) in the European population. However, pathogenic NFKB1 variants have never been reported in the Japanese population. We present a 29-year-old Japanese woman with CVID. A novel variant, c.136 C > T, p.(Gln46*), was identified in NFKB1. Her mother and daughter carried the same variant, demonstrating the first Japanese pedigree with an NFKB1 pathogenic variant.

  Mar. 2024, Human genome variation, 11(1) (1), 15 - 15, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 意識障害と片麻痺を繰り返した46,XX,der(18)t(12;18)(p11.2;p11.2)

  川村 葵, 山口 宏, 伊藤 立人, 曽根原 晶子, 洪 聖媛, 鮫島 智大, 花房 宏昭, 老川 静香, 徳元 翔一, 坊 亮輔, 永瀬 裕朗

  (一社)日本小児神経学会, Mar. 2024, 脳と発達, 56(2) (2), 151 - 151, Japanese


• 持続する右下肢痛で発症した骨肉腫の1例

  伊藤 立人, 川村 葵, 曽根原 晶子, 西村 明紘, 洪 聖媛, 鮫島 智大, 花房 宏昭, 老川 静香, 徳元 翔一, 山口 宏, 坊 亮輔, 山本 暢之, 永瀬 裕朗

  (一社)日本小児神経学会, Mar. 2024, 脳と発達, 56(2) (2), 152 - 152, Japanese


• 当院における小児心停止症例に対する遺伝学的診断(Genetic autopsy)を含めた原因究明システムの構築

  松井 鋭, 黒澤 寛史, 花房 宏昭, 洪本 加奈, 坊 亮輔, 森貞 直哉, 吉田 牧子, 笠井 正志, 林 卓郎, 竹井 寛和, 谷澤 直子, 大西 康裕, 大西 理史, 宮脇 康輔, 松本 泰右, 長崎 靖, 田中 亮二郎, 野津 寛大, 飯島 一誠

  (公社)日本小児科学会, Feb. 2024, 日本小児科学会雑誌, 128(2) (2), 293 - 293, Japanese


• Lysinuric protein intolerance exhibiting renal tubular acidosis/Fanconi syndrome in a Japanese woman

  Hiroaki Hanafusa, Katsuya Nakamura, Yuji Kamijo, Masashi Kitahara, Takashi Ehara, Tsuneaki Yoshinaga, Kaoru Aoki, Nagaaki Katoh, Tomomi Yamaguchi, Tomoki Kosho, Yoshiki Sekijima

  Abstract Lysinuric protein intolerance (LPI), caused by pathogenic variants of SLC7A7, is characterized by protein aversion, failure to thrive, hyperammonemia, and hepatomegaly. Recent studies have reported that LPI can cause multiple organ dysfunctions, including kidney disease, autoimmune deficiency, pulmonary alveolar proteinosis, and osteoporosis. We report the case of a 47‐year‐old Japanese woman who was initially diagnosed with renal tubular acidosis (RTA), Fanconi syndrome, and rickets. At the age of 3 years, she demonstrated a failure to thrive. Urinary amino acid analysis revealed elevated lysine and arginine levels, which were masked by pan‐amino aciduria. She was subsequently diagnosed with rickets at 5 years of age and RTA/Fanconi syndrome at 15 years of age. She was continuously treated with supplementation of vitamin D3, phosphate, and bicarbonate. A renal biopsy at 18 years of age demonstrated diffuse proximal and distal tubular damage with endocytosis‐lysosome pathway abnormalities. Distinctive symptoms of LPI, such as protein aversion and postprandial hyperammonemia were not observed throughout the patient's clinical course. The patient underwent a panel‐based comprehensive genetic testing and was diagnosed with LPI. As the complications of LPI involve many organs, patients lacking distinctive symptoms may develop various diseases, including RTA/Fanconi syndrome. Our case indicates that proximal and distal tubular damages are notable findings in patients with LPI. The possibility of LPI should be carefully considered in the management of RTA/Fanconi syndrome and/or incomprehensible pathological tubular damage, even in the absence of distinctive symptoms; furthermore, a comprehensive genetic analysis is useful for diagnosing LPI.

  Wiley, Sep. 2023, JIMD Reports

  Scientific journal


• Clinical utility of urinary mulberry bodies/cells testing in the diagnosis of Fabry disease.

  Katsuya Nakamura, Saki Mukai, Yuka Takezawa, Yuika Natori, Akari Miyazaki, Yuichiro Ide, Mayu Takebuchi, Kana Nanato, Mizuki Katoh, Harue Suzuki, Akiko Sakyu, Tomomi Kojima, Emiko Kise, Hiroaki Hanafusa, Tomoki Kosho, Koichiro Kuwahara, Yoshiki Sekijima

  INTRODUCTION: Variants in the galactosidase alpha (GLA) gene cause Fabry disease (FD), an X-linked lysosomal storage disorder caused by α-galactosidase A (α-GAL) deficiency. Recently, disease-modifying therapies have been developed, and simple diagnostic biomarkers for FD are required to initiate these therapies in the early stages of the disease. Detection of urinary mulberry bodies and cells (MBs/MCs) is beneficial for diagnosing FD. However, few studies have evaluated the diagnostic accuracy of urinary MBs/MCs in FD. Herein, we retrospectively evaluated the diagnostic ability of urinary MBs/MCs for FD. METHODS: We analyzed the medical records of 189 consecutive patients (125 males and 64 females) who underwent MBs/MCs testing. Out of these, two female patients had already been diagnosed with FD at the time of testing, and the remaining 187 patients were suspected of having FD and underwent both GLA gene sequencing and/or α-GalA enzymatic testing. RESULTS: Genetic testing did not confirm the diagnosis in 50 females (26.5%); hence, they were excluded from the evaluation. Two patients were previously diagnosed with FD, and sixteen were newly diagnosed. Among these 18 patients, 15, including two who had already developed HCM at diagnosis, remained undiagnosed until targeted genetic screening of at-risk family members of patients with FD was performed. The accuracy of urinary MBs/MCs testing exhibited a sensitivity of 0.944, specificity of 1, positive predictive value of 1, and negative predictive value of 0.992. CONCLUSIONS: MBs/MCs testing is highly accurate in diagnosing FD and should be considered during the initial evaluation prior to genetic testing, particularly in female patients.

  Sep. 2023, Molecular genetics and metabolism reports, 36, 100983 - 100983, English, International magazine

  Scientific journal


• MSL3領域のヌリソミーで生じたBasilicata-Akhtar症候群の日本人男児例(Basilicata-Akhtar syndrome derived from a nullisomy of the MSL3 region in a Japanese boy)

  花房 宏昭, 森貞 直哉, 長坂 美和子, 叶 明娟, 野口 裕子, 長野 智那, 野津 寛大, 粟野 宏之

  Basilicata-Akhtar症候群はMSL3のヘテロ接合性もしくはヘミ接合性変異によるまれなX連鎖性疾患で乳児期からの全般性発達遅滞,経口摂取障害,筋緊張低下などを特徴とする.これまでに約40例が報告されているが,本邦では報告されていない.今回,本邦初のBasilicata-Akhtar症候群の例を報告する.症例は日本人の7歳男児で全般性発達遅滞,筋緊張の低下,経口摂取障害を呈した.身体所見として内眼角贅皮,眼角解離,眼瞼裂斜下,広い鼻梁,上向きの鼻孔,テント状の上口唇,垂れた耳,短い手足,先細りの指,外反膝,扁平足,胸郭変形,側彎を認めた.アレイCGH解析で,MSL3の全コード領域と,ARHGAP6の5'側のみを含んだXp22.2のヘミ接合性欠失を認めた.本症例の表現型はこれまでに報告されているBasilicata-Akhtar症候群に一致するものであった.本症例の病態は機能喪失を引き起こすMSL3の全コード領域の欠失であった.本症例と同様にMSL3の全コード領域とARHGAP6の5'領域のみを欠失するBasilicata-Akhtar症候群の女児2例の報告があるが,ヌリソミー男児例は過去に報告がない.この欠失を有する3例とMSL3の一塩基バリアントを有する既報告例との間に,臨床症状の違いは認められなかった.本症候群の機能的特徴を明らかにするためには,多様な民族から様々なバリアントを持つ症例をさらに集積することが重要である.(著者抄録)

  (一社)日本小児神経学会, Jul. 2023, 脳と発達, 55(4) (4), 279 - 282, English


• MSL3領域のヌリソミーで生じたBasilicata-Akhtar症候群の日本人男児例(Basilicata-Akhtar syndrome derived from a nullisomy of the MSL3 region in a Japanese boy)

  花房 宏昭, 森貞 直哉, 長坂 美和子, 叶 明娟, 野口 裕子, 長野 智那, 野津 寛大, 粟野 宏之

  Basilicata-Akhtar症候群はMSL3のヘテロ接合性もしくはヘミ接合性変異によるまれなX連鎖性疾患で乳児期からの全般性発達遅滞,経口摂取障害,筋緊張低下などを特徴とする.これまでに約40例が報告されているが,本邦では報告されていない.今回,本邦初のBasilicata-Akhtar症候群の例を報告する.症例は日本人の7歳男児で全般性発達遅滞,筋緊張の低下,経口摂取障害を呈した.身体所見として内眼角贅皮,眼角解離,眼瞼裂斜下,広い鼻梁,上向きの鼻孔,テント状の上口唇,垂れた耳,短い手足,先細りの指,外反膝,扁平足,胸郭変形,側彎を認めた.アレイCGH解析で,MSL3の全コード領域と,ARHGAP6の5'側のみを含んだXp22.2のヘミ接合性欠失を認めた.本症例の表現型はこれまでに報告されているBasilicata-Akhtar症候群に一致するものであった.本症例の病態は機能喪失を引き起こすMSL3の全コード領域の欠失であった.本症例と同様にMSL3の全コード領域とARHGAP6の5'領域のみを欠失するBasilicata-Akhtar症候群の女児2例の報告があるが,ヌリソミー男児例は過去に報告がない.この欠失を有する3例とMSL3の一塩基バリアントを有する既報告例との間に,臨床症状の違いは認められなかった.本症候群の機能的特徴を明らかにするためには,多様な民族から様々なバリアントを持つ症例をさらに集積することが重要である.(著者抄録)

  (一社)日本小児神経学会, Jul. 2023, 脳と発達, 55(4) (4), 279 - 282, English


• Dravet syndrome and hemorrhagic shock and encephalopathy syndrome associated with an intronic deletion of SCN1A.

  Hiroaki Hanafusa, Hiroshi Yamaguchi, Hidehito Kondo, Miwako Nagasaka, Ming Juan Ye, Shizuka Oikawa, Shoichi Tokumoto, Kazumi Tomioka, Masahiro Nishiyama, Naoya Morisada, Masafumi Matsuo, Kandai Nozu, Hiroaki Nagase

  OBJECTIVE: Hemorrhagic shock and encephalopathy syndrome (HSES) is a serious condition that requires intensive care and is associated with a high mortality rate. However, its pathogenesis remains unclear. In the present study, a genetic analysis was performed to determine the genetic background of patients with clinically suspected Dravet syndrome (DS) who developed HSES. METHODS: Whole exome sequencing was performed, followed by minigene analysis of the intron variant detected by whole exome sequencing to confirm its effect on splicing. RESULTS: Whole exome sequencing revealed a novel 21-bp deletion in intron 3 of SCN1A NM_001165963.4 (NC_000002.11:g.166073675_166073695del). This deletion was not found in the patient's parents and was proven to be de novo. Minigene analysis revealed an aberrant mRNA lacking 40 and 106 bp from the 5' end of exon 4 of SCN1A. Therefore, we diagnosed this case as DS due to the deletion in intron 3 of SCN1A. CONCLUSIONS: We report a case of DS with HSES caused by a 21-bp deletion in the intron of SCN1A that was confirmed by minigene analysis. The present case met Levin's criteria for HSES and the splicing analysis of SCN1A is an important finding. This study has important implications for understanding HSES pathogenesis.

  Jun. 2023, Brain & development, 45(6) (6), 317 - 323, English, International magazine

  Scientific journal


• Germ-cell-specific transcriptome analysis illuminates the chromatin and ubiquitin pathway in autism spectrum disorders.

  Sawako Furukawa, Jun Nomura, Hiroaki Hanafusa, Hiroko Maegawa, Toru Takumi

  Accumulating epidemiological studies have suggested a positive association between advanced paternal age at conception and the increased risk of neurodevelopmental outcomes such as autism spectrum disorder (ASD) in their children. Recent biological studies using human sperm have identified increased de novo mutations in aged fathers, and hyper- or hypomethylation has been identified in the sperm from aged rodents. Dysregulation of DNA methylation in sperm may explain the transgenerational effects on the pathogenesis of ASD. However, compared to these epigenetic changes in the sperm of aged males, the effects of inherited predisposition from germ cells are largely unknown. Here, we use single-cell transcriptome data sets from 13 cell lines, including 12 ASD-associated CNVs models and control, that are performed neural differentiation from mouse embryonic stem cells. This study performed comprehensive bioinformatic analyses such as gene ontology (GO), network, pathway, and upstream regulator analyses. Through these analyses, we identify several susceptible pathways, such as chromatin and ubiquitin, in addition to translational and oxidative phosphorylation. Our results suggest that dysregulation of epigenetic chromosome remodeling and ubiquitin-proteasome pathway in the germ cell is a possible modulator for subsequent differentiated cells, sperm, and egg, as a risk factor for the neurodevelopmental disorder.

  Jun. 2023, Autism research : official journal of the International Society for Autism Research, 16(6) (6), 1101 - 1110, English, International magazine

  Scientific journal


• 有熱性てんかん重積・急性脳症に対する疾患関連遺伝子の探索

  山口 宏, 花房 宏昭, 老川 静香, 徳元 翔一, 冨岡 和美, 西山 将広, 森貞 直哉, 野津 寛大, 永瀬 裕朗

  (一社)日本小児神経学会, May 2023, 脳と発達, 55(Suppl.) (Suppl.), S318 - S318, Japanese


• 出血性ショック脳症症候群をきたしたDravet症候群にSCN1Aのイントロンに新規の21塩基欠失を認めminigene解析を実施した1例

  花房 宏昭, 山口 宏, 老川 静香, 徳元 翔一, 冨岡 和美, 西山 将広, 長坂 美和子, 近藤 秀仁, 森貞 直哉, 松尾 雅文, 野津 寛大, 永瀬 裕朗

  (一社)日本小児神経学会, May 2023, 脳と発達, 55(Suppl.) (Suppl.), S302 - S302, Japanese


• 当院での脳症関連遺伝子パネルを用いた疾患関連遺伝子の同定の試み

  山口 宏, 花房 宏昭, 徳元 翔一, 冨岡 和美, 西山 将広, 森貞 直哉, 野津 寛大, 永瀬 裕朗

  (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 628 - 628, Japanese


• Impact after the Change from Voluntary to Universal Oral Rotavirus Vaccination on Consecutive Emergency Department Visits for Acute Gastroenteritis among Children in Kobe City, Japan (2016-2022).

  Hiroshi Yamaguchi, Kandai Nozu, Hiroaki Hanafusa, Yoshinori Nambu, Takumi Kido, Atsushi Kondo, Akihiro Tamura, Hiroyuki Awano, Ichiro Morioka, Hiroaki Nagase, Akihito Ishida

  Rotavirus (RV) is the leading cause of acute gastroenteritis (AGE), particularly in infants. In 2006, the high efficacy of oral RV vaccines (RVVs, RotarixTM and RotaTeqTM) was demonstrated. Voluntary RVV started in Japan in 2011, and in October 2020 were launched as universal oral RVVs in Japan. However, the impact of changes from voluntary to universal RVVs has not been studied in a primary emergency medical center in Japan. We investigated changes in the number of pediatric patients with AGE after introducing universal RVVs in our center. A clinical database of consecutive patients aged <16 who presented to Kobe Children’s Primary Emergency Medical Center between 1 April 2016 and 30 June 2022 was reviewed. After implementing universal RVVs, fewer children presented with RV-associated AGE (the reduction of proportion of the patients in 2022 was −61.7% (all ages), −57.9% (<1 years), −67.8% (1−<3 years), and −61.4% (3−<5 years) compared to 2019). A similar decrease in those of age who were not covered by the universal RVV was observed. There was a significant decline in the number of patients with AGE during the RV season who presented to the emergency department after implementing universal RVVs.

  Oct. 2022, Vaccines, 10(11) (11), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Influence of UGT1A1 Genetic Variants on Free Bilirubin Levels in Japanese Newborns: A Preliminary Study.

  Hiroaki Hanafusa, Shinya Abe, Shohei Ohyama, Yuki Kyono, Takumi Kido, Ruka Nakasone, Mariko Ashina, Kenji Tanimura, Kandai Nozu, Kazumichi Fujioka

  BACKGROUND: Free bilirubin (Bf) is a better marker than total serum bilirubin (TSB) for predicting bilirubin encephalopathy (BE). To date, two UGT1A1 genetic variants (rs4148323 and rs3064744) have been associated with neonatal hyperbilirubinemia; however, the direct association between UGT1A1 variants and Bf levels in newborns has not been elucidated. METHODS: We retrospectively analyzed the clinical data of 484 infants, including the genotype data of two UGT1A1 genetic variants. We divided the infants into a high Bf group (Bf ≥ 1.0 µg/dL, n = 77) and a non-high Bf group (Bf < 1.0 µg/dL, n = 407), based on the peak Bf values. Logistic regression analysis was performed to calculate the odds ratios (ORs) for each variant allele compared to wild-type alleles. RESULTS: The frequencies of the A allele in rs4148323 and (TA)7 allele in rs3064744 in the high Bf group (29% and 4%, respectively) were significantly different from those in the non-high Bf group (16% and 12%, respectively). In logistic regression analysis, for rs4148323, the A allele was significantly associated with an increased risk of hyper-free bilirubinemia over the G allele (adjusted OR: 1.80, 95% confidence interval [CI]: 1.19-2.72, p < 0.01). However, for rs3064744, the (TA)7 allele was significantly associated with a decreased risk of hyper-free bilirubinemia over the (TA)6 allele (adjusted OR: 0.42, 95% CI: 0.18-0.95, p = 0.04). CONCLUSIONS: This study is the first to show that the A allele in rs4148323 is a risk factor and that the (TA)7 allele in rs3064744 is a protective factor for developing hyper-free bilirubinemia in Japanese newborns.

  Oct. 2022, International journal of environmental research and public health, 19(20) (20), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• てんかん重積状態・急性脳症における疾患原因遺伝子の同定の試み

  山口 宏, 花房 宏昭, 徳元 翔一, 冨岡 和美, 西山 将広, 森貞 直哉, 野津 寛大, 永瀬 裕朗

  (一社)日本てんかん学会, Aug. 2022, てんかん研究, 40(2) (2), 410 - 410, Japanese


• Heterozygous missense variant in TRPC6 in a boy with rapidly progressive infantile nephrotic syndrome associated with diffuse mesangial sclerosis.

  Hiroaki Hanafusa, Yoshihiko Hidaka, Tomomi Yamaguchi, Hisashi Shimojo, Takanori Tsukahara, Tsubasa Murase, Daisuke Matsuoka, Nao Chiba, Shun Shimada, Hirokazu Morokawa, Norio Omori, Hironori Minoura, China Nagano, Kyoko Takano, Katsuya Nakamura, Keiko Wakui, Yoshimitsu Fukushima, Takeshi Uehara, Yozo Nakazawa, Kazumoto Iijima, Kandai Nozu, Tomoki Kosho

  Transient receptor potential channel C6 encoded by TRPC6 is involved in slit diaphragm formation in podocytes, and abnormalities of the TRPC6 protein cause various glomerular diseases. The first identified pathogenic variant of TRPC6 was found to cause steroid-resistant nephrotic syndrome that typically developed in adulthood and then slowly led to end-stage renal disease, along with a renal pathology of focal segmental glomerulosclerosis. Here, we report a patient with rapidly progressing infantile nephrotic syndrome and a heterozygous missense TRPC6 variant. The patient, a 2-year-old Japanese boy, developed steroid-resistant nephrotic syndrome at age 11 months. His renal function deteriorated rapidly, and peritoneal dialysis was introduced at age 1 year and 6 months. His renal pathology, obtained at age 1 year and 1 month, was consistent with diffuse mesangial sclerosis (DMS). Clinical exome analysis and custom panel analysis for hereditary renal diseases revealed a reported heterozygous missense variant in TRPC6 (NM_004621.5:c.523C > T:p.Arg175Trp). This is the first report of a patient with a TRPC6-related renal disorder associated with DMS.

  Jul. 2021, American journal of medical genetics. Part A, 185(7) (7), 2175 - 2179, English, International magazine


• A Japanese boy with NAA10-related syndrome and hypertrophic cardiomyopathy.

  Ayumi Shishido, Naoya Morisada, Kenta Tominaga, Hiroyasu Uemura, Akiko Haruna, Hiroaki Hanafusa, Kandai Nozu, Kazumoto Iijima

  NAA10-related syndrome is an extremely rare X-chromosomal disorder, the symptoms of which include intellectual disability (ID), ocular anomalies, or congenital heart diseases, such as hypertrophic cardiomyopathy (HCM). Here, we describe a 4-year-old Japanese male patient who exhibited mild ID, HCM, and specific facial features. A hemizygous mutation (NM_003491.3: c.455_458del, p. Thr152Argfs*6) in exon 7 of NAA10 was detected. We recommend that patients undergo precise medical follow-up considering the characteristics of NAA10-related syndrome.

  2020, Human genome variation, 7, 23 - 23, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• A girl with CLOVES syndrome with a recurrent PIK3CA somatic mutation and pancreatic steatosis.

  Hiroaki Hanafusa, Naoya Morisada, Tadashi Nomura, Daisuke Kobayashi, Yoshinobu Akasaka, Ming Juan Ye, Kandai Nozu, Noriyuki Nishimura, Kazumoto Iijima, Hideto Nakao

  CLOVES syndrome is characterized by congenital lipomatous overgrowth, vascular malformation, epidermal nevi, and scoliosis/spinal malformation. It is caused by somatic mosaicism of gain-of-function variants of PIK3CA. Here, we describe a novel case of a 5-year-old Japanese girl with CLOVES and concurrent pancreatic steatosis. She had a recurrent somatic mutation in PIK3CA (NM_006218.3: c.1357G>A, p.Glu453Lys), elevated HbA1c levels, and pancreatic steatosis. This case indicates that pancreatic screening is critical for PIK3CA-related disorders.

  2019, Human genome variation, 6, 31 - 31, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• The smallest de novo 20q11.2 microdeletion causing intellectual disability and dysmorphic features.

  Hiroaki Hanafusa, Naoya Morisada, Yusuke Ishida, Ryosuke Sakata, Keiichi Morita, Shizu Miura, Ming Juan Ye, Toshiyuki Yamamoto, Nobuhiko Okamoto, Kandai Nozu, Kazumoto Iijima

  The 20q11.2 microdeletion is a rare chromosomal aberration characterized by intellectual disability (ID), motor developmental delay, neonatal feeding problems, and facial dysmorphism. Here, a 2-year- and 6-month-old Japanese girl with a 1.2 Mb microdeletion of 20q11.2 showed ID, motor developmental delay, and distinctive facial features without feeding problems. The deleted region was identified by array-based comparative genomic hybridization and is the smallest reported for a 20q11.2 microdeletion.

  2017, Human genome variation, 4, 17050 - 17050, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)

• 拡大新生児マススクリーニングで診断されたSMN2遺伝子4コピーのSMAに対して発症前治療を行った1例

  曽根原 晶子, 坊 亮輔, 洪 聖媛, 南部 静紀, 花房 宏昭, 李 知子, 竹島 泰弘, 西尾 久英, 粟野 宏之

  (一社)日本マススクリーニング学会, Aug. 2023, 日本マス・スクリーニング学会誌, 33(2) (2), 260 - 260, Japanese


• 拡大新生児マススクリーニングで診断されたSMN2遺伝子4コピーのSMAに対して発症前治療を行った1例

  曽根原 晶子, 坊 亮輔, 洪 聖媛, 南部 静紀, 花房 宏昭, 李 知子, 竹島 泰弘, 西尾 久英, 粟野 宏之

  (一社)日本マススクリーニング学会, Aug. 2023, 日本マス・スクリーニング学会誌, 33(2) (2), 260 - 260, Japanese


• がんゲノムプロファイル検査でRAD51Dが検出され、事前のリスク低減卵管卵巣摘出術についての情報交換が有用であった症例

  花房 宏昭, 田中 敬子, 濱 真奈美, 金原 史朗, 益子 尚久, 坊 亮輔, 國久 智成, 粟野 宏之, 清田 尚臣, 久保 亮治, 南 博信, 野津 寛大

  (一社)日本遺伝カウンセリング学会, Jun. 2023, 日本遺伝カウンセリング学会誌, 44(2) (2), 139 - 139, Japanese


• NIPTの実施週数に検討を要したVanishing Twin妊娠2例について

  濱 真奈美, 花房 宏昭, 田中 敬子, 冨本 雅子, 尾崎 可奈, 今福 仁美, 坊 亮輔, 國久 智成, 久保 亮治, 粟野 宏之, 野津 寛大

  (一社)日本遺伝カウンセリング学会, Jun. 2023, 日本遺伝カウンセリング学会誌, 44(2) (2), 149 - 149, Japanese


• 非認証機関でのNIPTで47,XXYもしくは47,XYYの可能性が指摘され、羊水染色体検査で正常核型の診断となった1例

  益子 尚久, 花房 宏昭, 濱 真奈美, 田中 敬子, 前田 美亜, 冨本 雅子, 今福 仁美, 粟野 宏之, 出口 雅士, 寺井 義人, 野津 寛大

  (一社)日本遺伝カウンセリング学会, Jun. 2023, 日本遺伝カウンセリング学会誌, 44(2) (2), 156 - 156, Japanese


• 無精子症の精査を契機に染色分体早期解離(PCS)が判明した夫婦へ遺伝カウンセリングを行った1例

  田中 敬子, 花房 宏昭, 濱 真奈美, 千葉 公嗣, 坊 亮輔, 國久 智成, 久保 亮治, 粟野 宏之, 野津 寛大

  (一社)日本遺伝カウンセリング学会, Jun. 2023, 日本遺伝カウンセリング学会誌, 44(2) (2), 163 - 163, Japanese


• ヌシネルセン治療を4年間行った脊髄性筋萎縮症3型の大腿MRIの変化

  池谷 紀衣子, 坊 亮輔, 曽根原 晶子, 花房 宏昭, 南部 静紀, 西尾 久英, 橋村 宏美, 粟野 宏之

  (一社)日本小児神経学会, May 2023, 脳と発達, 55(Suppl.) (Suppl.), S323 - S323, Japanese


• 【小児外科疾患に関連する症候群】Waardenburg症候群

  亀岡 泰幸, 花房 宏昭, 大片 祐一, 岩渕 瀬怜奈, 吉村 翔平, 渡部 彩, 植村 光太郎, 冨岡 雄一郎, 鮫島 由友, 中井 優美子, 尾藤 祐子

  (株)東京医学社, Apr. 2023, 小児外科, 55(4) (4), 454 - 457, Japanese


• 死亡時のアシルカルニチン分析結果を契機に確定診断したグルタル酸血症2型の一例

  坊 亮輔, 池谷 紀衣子, 花房 宏昭, 南部 静紀, 奥谷 貴弘, 野津 寛大, 粟野 宏之

  (一社)日本先天代謝異常学会, Oct. 2022, 日本先天代謝異常学会雑誌, 38, 193 - 193, Japanese


• 糖原病9a型の3家系6人における食事療法開始後の身長の推移

  池谷 紀衣子, 坊 亮輔, 洪 聖媛, 花房 宏昭, 南部 静紀, 粟野 宏之

  (一社)日本先天代謝異常学会, Oct. 2022, 日本先天代謝異常学会雑誌, 38, 215 - 215, Japanese


• 【小児の腎疾患を見つめ直す--基礎と臨床】腎疾患の遺伝子解析

  森貞 直哉, 洪本 加奈, 花房 宏昭, 田中 悠

  ＜文献概要＞本稿では遺伝性腎疾患のゲノム医療の現状について述べる.わが国では胎児超音波検査や学校検尿が広く行われており,これらを契機に先天性腎尿路異常(CAKUT)や慢性糸球体腎炎,多発性嚢胞腎(PKD)などの慢性腎疾患(CKD)が発見されることがある.小児CKDは遺伝子の異常により発症することが多いとされており,小児腎疾患患者を診療するうえでゲノム医療に関する知識は必須である.近年では次世代シークエンサーによる網羅的解析が主流となっているが,網羅的解析にはさまざまな留意点があり,遺伝カウンセリングを併せて行うことが重要である.

  金原出版(株), Jun. 2022, 小児科, 63(6) (6), 583 - 588, Japanese


• ファブリー病女性at risk者の診断や治療選択の意思決定に影響する因子の検討

  黄瀬 恵美子, 中村 勝哉, 石川 真澄, 阪下 達哉, 花房 宏昭, 古庄 知己

  (一社)日本遺伝カウンセリング学会, Jun. 2021, 日本遺伝カウンセリング学会誌, 42(2) (2), 95 - 95, Japanese


• Genetic counseling and treatment outcome of a Japanese family with Fabry disease showing intrafamilial variation

  中村勝哉, 中村勝哉, 中村勝哉, 黄瀬恵美子, 黄瀬恵美子, 石川真澄, 阪下達哉, 花房宏昭, 関島良樹, 古庄知己, 古庄知己

  (一社)日本遺伝カウンセリング学会, 2021, 日本遺伝カウンセリング学会誌, 42(2) (2), 100 - 100, Japanese


• 【ゲノム革命-予防・医療のイノベーション】ゲノム医療の提供体制構築と人材育成

  花房 宏昭, 古庄 知己

  ＜文献概要＞ポイント ◆遺伝・ゲノム医療は,がん遺伝子パネル検査の実施などをきっかけに大きく発展しようとしている.◆生殖細胞系の遺伝・ゲノム情報を扱うには,その特殊性を考慮した繊細な対応が必要である.◆遺伝・ゲノム医療に主に携わる専門的人材として,臨床遺伝専門医や認定遺伝カウンセラーなどがある.

  (株)医学書院, Apr. 2020, 公衆衛生, 84(4) (4), 226 - 231, Japanese

• Influence of genetic variants on unbound bilirubin levels in Japanese newborns: a preliminary study

  The 22nd Congress of the Federation of Asia and Oceania Perinatal Societies, Oct. 2023, English

  Oral presentation


• TRPC6 pathogenic variant in a Japanese boy with infantile nephrotic syndrome

  ASHG 2019 Annual Meeting, English

  Poster presentation