Article
Medicine, Research & Experimental
Y. Gloor, C. Lloret-Linares, M. Bosilkovska, N. Perroud, H. Richard-Lepouriel, J. -m. Aubry, Y. Daali, J. A. Desmeules, M. Besson
Summary: Cytochromes from the P450 family have a central role in the metabolism of antidepressants, but the variability in drug metabolic capacities among individuals can present risks and complicate drug prescription. This study investigates the genetic and environmental factors contributing to decreased cytochrome activities in a cohort of antidepressant-treated patients. The results reveal a significant rate of phenoconversion and reduced activities of certain cytochromes, highlighting the importance of phenotyping and the risks in a polymedicated population.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Muhammad Nurhafizuddin, Aziemah Azizi, Long Chiau Ming, Naeem Shafqat
Summary: This study analyzed the protein crystal structure of cytochrome P450 oxidoreductase (POR) to investigate the effects of mutations on enzyme structure. The findings highlight the significance of POR cofactor binding sites in electron transfer to the CYP450 enzyme family, as missense mutations in these sites can lead to severe forms of cytochrome P450 oxidoreductase deficiency (PORD).
Article
Pharmacology & Pharmacy
Junichi Nakagawa, Takahiko Kinjo, Naoya Aiuchi, Kayo Ueno, Hirofumi Tomita, Takenori Niioka
Summary: This study examined the impact of gene polymorphisms on the plasma concentration of apixaban. The results showed that decreased creatinine clearance and the PXR*1B/*1B haplotype were associated with increased plasma concentration of apixaban, while the presence of the POR*28 allele was associated with decreased plasma concentration of apixaban.
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Oncology
Hong Jiacong, Yang Qirui, Li Haonan, Song Yichang, Chen Yan, Chen Keng
Summary: Osteosarcoma is the most common primary bone cancer in adolescents with a poor prognosis. Current treatments are not satisfactory, therefore, it is critical to develop novel therapeutic strategies. This study discovered that zoledronic acid (ZOL) induces ferroptosis by upregulating POR expression in osteosarcoma cells. Knockdown of POR attenuated ZOL-induced cytotoxicity and the effect of ferroptosis. ZOL also inhibits osteosarcoma growth in vivo. These findings suggest that POR could be used as a therapeutic target to inhibit osteosarcoma.
Article
Genetics & Heredity
Xudong Wang, Zhongmin Xia, Ying He, Xiaoman Zhou, Haixia Zhang, Chunliu Gao, Yunsheng Ge, Xiaofang Cai, Yulin Zhou, Qiwei Guo
Summary: This study evaluated the profile of G6PD deficiency in Xiamen, China, finding a prevalence of 1.39% and identifying 12 variants and 32 genotypes, with the six most common variants accounting for approximately 94% of the identified alleles. The use of genotyping helped confirm the presence of pathogenic G6PD variants and improve the accuracy of newborn screening, with cold-chain transportation significantly enhancing the positive predictive value (PPV).
FRONTIERS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Bin Li, Zheng Wang, Qian Chen, Kuokuo Li, Xiaomeng Wang, Yijing Wang, Qian Zeng, Ying Han, Bin Lu, Yuwen Zhao, Rui Zhang, Li Jiang, Hongxu Pan, Tengfei Luo, Yi Zhang, Zhenghuan Fang, Xuewen Xiao, Xun Zhou, Rui Wang, Lu Zhou, Yige Wang, Zhenhua Yuan, Lu Xia, Jifeng Guo, Beisha Tang, Kun Xia, Guihu Zhao, Jinchen Li
Summary: To address the challenge of accessing detailed clinical phenotypic features of patients with genetic variants, researchers developed an online database called GPCards, which integrates genetic and clinical data to provide interpretation of genotype-phenotype correlations and prioritization of candidate functional variants. This tool accelerates the interpretation of genotype-phenotype correlations in human genetic diseases and aids researchers in making faster diagnostic and treatment decisions.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Review
Genetics & Heredity
Lili Yang, Xiaoli Shu, Shujiong Mao, Yi Wang, Xiaonan Du, Chaochun Zou
Summary: Angelman syndrome is a rare neurodevelopmental disease caused by the loss of function of the maternal copy of UBE3A. It is characterized by developmental delay, intellectual disability, lack of speech, and ataxia. Different genetic types may show different phenotypes, and understanding genotype-phenotype correlations can lead to individualized treatment options.
Article
Electrochemistry
Celia M. Silveira, Patricia R. Rodrigues, Wissam Ghach, Sofia A. Pereira, Francisco Esteves, Michel Kranendonk, Mathieu Etienne, M. Gabriela Almeida
Summary: The study investigated the direct electrochemical response of membrane-bound human cytochrome P450 1A2 on pyrolytic graphite electrodes encapsulated in a sol-gel matrix. It showed that CYP1A2 is highly sensitive to O-2 and easily inactivated under aerobic conditions, but remains active when in the presence of its electron donor partner, cytochrome P450 oxidoreductase (CPR). This highlights the crucial role of CPR in stabilizing the immobilized CYP1A2 enzyme and preserving O-2 electrocatalysis in this electrochemical set-up.
Article
Genetics & Heredity
Laurien Vaes, Daisy Rymen, David Cassiman, Anna Ligezka, Nele Vanhoutvin, Dulce Quelhas, Eva Morava, Peter Witters
Summary: PMM2-CDG is a rare disease that affects the glycosylation of proteins, leading to impaired functionality. A retrospective cohort study on 26 PMM2-CDG patients revealed different pathogenic variants of the genotype can impact disease severity differently. Variants involving specific domains can result in a less severe or worse clinical course, offering insights into the phenotypic prognosis of PMM2-CDG.
Article
Engineering, Biomedical
Chase P. Monckton, Aidan Brougham-Cook, Gregory H. Underhill, Salman R. Khetani
Summary: In this study, researchers used high-throughput ECM microarrays and high content imaging to evaluate the attachment and differentiated functions of iPSC-derived human hepatocyte-like cells (iHep) on different liver ECM protein combinations. They discovered that the responses of iHep are regulated by the cooperation between ECM stiffness and protein composition. By selectively coating ECM proteins on materials with physiological stiffness, they achieved higher levels of mature functions in iHep cultures compared to primary human hepatocyte cultures, which has implications for drug screening, disease modeling, and regenerative medicine.
ACTA BIOMATERIALIA
(2022)
Article
Biology
Sarah Charnaud, Jacob E. Munro, Lucie Semenec, Ramin Mazhari, Jessica Brewster, Caitlin Bourke, Shazia Ruybal-Pesantez, Robert James, Dulcie Lautu-Gumal, Harin Karunajeewa, Ivo Mueller, Melanie Bahlo
Summary: The CYP2D6 enzyme is responsible for metabolizing 25% of commonly used pharmaceuticals and its gene typing is of great interest in pharmacogenetics due to its polymorphic nature. Accurate allele typing of the CYP2D6 gene has been challenging due to copy number variants and pseudogenes. This study presents a robust data processing pipeline called PLASTER for accurate allele typing using long-read sequencing. This pharmacogenetic method has the potential to improve drug safety and efficacy through screening prior to drug administration.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yuan Gao, Jingjing Ma
Summary: This study found that the A503V polymorphism can affect the metabolism of tacrolimus catalyzed by CYP3A5, and may serve as a potential biomarker for tacrolimus treatment in transplantation recipients.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yvonne Carius, Michael Hutter, Flora Kiss, Rita Bernhardt, C. Roy D. Lancaster
Summary: This study revealed the crystal structure of cytochrome P450 CYP106A1 from Priestia megaterium, which shows a rare sixth beta-sheet. Comparison with the previously studied CYP106A2 and docking studies with the substrate cortisol revealed a different orientation of the steroid molecule in the active sites, explaining the observed differences in substrate conversion and product formation by the two enzymes.
Review
Biochemistry & Molecular Biology
Maria Alcazar-Fabra, Francisco Rodriguez-Sanchez, Eva Trevisson, Gloria Brea-Calvo
Summary: Primary Coenzyme Q deficiencies present with diverse clinical manifestations and lack clear genotype-phenotype correlations, making diagnosis and prognosis challenging. By analyzing symptoms and patients described in existing literature, new associations between age of symptom onset and pathogenic variants have been identified, providing potential guidance for diagnosis and treatment. The development of an online platform to compile and update clinical information on CoQ deficiencies could serve as a valuable resource for clinicians in the future.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Endocrinology & Metabolism
Jin Zhang, Kwan Leong Woo, Yongxiong Hai, Shimin Wang, Ying Lin, Ying Huang, Xiaofang Peng, HongShi Wu, Shaoling Zhang, Li Yan, Yan Li
Summary: This article aims to raise awareness of Cytochrome P450 Oxidoreductase Deficiency (PORD) through a case study of a pregnant woman with symptoms of virilization. The case description details the patient's symptoms, medical history, and genetic test results. The discussion reviews the clinical manifestations, diagnosis, and treatment options for PORD, emphasizing the importance of considering rare causes like PORD in pregnant women with abnormal virilization symptoms. This study also identifies a novel mutation in the Chinese population.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Genetics & Heredity
Tomoko Fuke, Akie Nakamura, Takanobu Inoue, Sayaka Kawashima, Kaori Hara-Isono, Keiko Matsubara, Shinichiro Sano, Kazuki Yamazawa, Maki Fukami, Tsutomu Ogata, Masayo Kagami
Summary: A study conducted genetic analysis in 173 patients meeting NH-CSS criteria, revealing that H19LOM and UPD(7)mat are common etiologies of SRS. Patients with all six NH-CSS items were most frequently associated with these two causes. The study confirmed the suitability of NH-CSS as clinical diagnostic criteria for SRS, showed the (epi)genetic heterogeneity of SRS, and demonstrated the necessity for further discussion on the SRS spectrum.
JOURNAL OF HUMAN GENETICS
(2022)
Article
Clinical Neurology
Yuki Kuranari, Tomoru Miwa, Maya Kono, Hironori Shibata, Tomohiro Ishii, Tomonobu Hasegawa
Summary: This paper presents an extremely rare case of an intracranial germinoma in the lateral ventricle, highlighting the challenges in diagnosis and the importance of literature review to improve awareness of germinomas in atypical locations.
CHILDS NERVOUS SYSTEM
(2023)
Editorial Material
Pediatrics
Takeshi Sato, Satsuki Nakano, Arihiko Kanaji, Tomohiro Ishii, Tomonobu Hasegawa
CONGENITAL ANOMALIES
(2023)
Letter
Genetics & Heredity
Kyoko Fukahori, Kaori Yamoto, Hirotomo Saitsu, Tsutomu Ogata, Keisuke Nagasaki
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Developmental Biology
Toyohide Endo, Miho Iida, Yosuke Ichihashi, Maki Oishi, Satoru Ikenoue, Yoshifumi Kasuga, Takeshi Sato, Mariko Hida, Tomohiro Ishii, Hiroshi Asanuma, Tomonobu Hasegawa, Mamoru Tanaka, Daigo Ochiai
Summary: The study found that fetal growth restriction and single umbilical artery are independent prenatal predictors of the development of hypospadias, and fetal vascular malperfusion of the placenta may be involved in the etiology of hypospadias.
Article
Endocrinology & Metabolism
Yuki Ishinoda, Asuka Uto, Yoshifumi Yamada, Maki Okazaki, Hidetomo Asada, Seina Wakamatsu, Isao Kurihara, Hironori Shibata, Tomohiro Ishii, Tomonobu Hasegawa, Hiroo Kumagai, Akira Kasuga
Summary: 17-alpha-hydroxylase deficiency (17OHD) can resemble primary aldosteronism (PA). The combination of a high aldosterone/renin ratio (ARR) and low cortisol level should trigger the consideration of 17OHD.
BMC ENDOCRINE DISORDERS
(2022)
Article
Biochemistry & Molecular Biology
Yuko Katoh-Fukui, Atsushi Hattori, Ruogu Zhang, Miho Terao, Shuji Takada, Kazuhiko Nakabayashi, Kenichiro Hata, Yutaka Yamada, Nobuo Matsuura, Maki Fukami
Summary: This study reports a case of pituitary gigantism in a Japanese woman who carried a heterozygous deletion at 20q11.23. The deletion resulted in overexpression of GHRH, leading to the extreme phenotype of excessive body growth.
HUMAN MOLECULAR GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Noriyuki Azuma, Tadashi Yokoi, Taku Tanaka, Emiko Matsuzaka, Yuki Saida, Sachiko Nishina, Miho Terao, Shuji Takada, Maki Fukami, Kohji Okamura, Kayoko Maehara, Tokiwa Yamasaki, Jun Hirayama, Hiroshi Nishina, Hiroshi Handa, Yuki Yamaguchi
Summary: This study reports the molecular and genetic characterization of Integrator complex subunit 15 (INTS15). INTS15 is highly expressed in the eye and brain, and it interacts with the Integrator complex to support small nuclear RNA 3' end processing. Knockdown of INTS15 leads to missplicing of numerous genes and affects genes associated with eye and brain development.
HUMAN MOLECULAR GENETICS
(2023)
Article
Genetics & Heredity
Takuya Hiraide, Kenji Shimizu, Yoshinori Okumura, Sachiko Miyamoto, Mitsuko Nakashima, Tsutomu Ogata, Hirotomo Saitsu
Summary: The recent use of genome sequencing in genetic analysis has led to the discovery of pathogenic variants located deep within introns. In this study, a Japanese boy with Joubert syndrome was found to have biallelic TCTN2 variants. Exome sequencing identified one variant, and subsequent genome sequencing found a deep intronic variant. Machine learning algorithms were unable to predict the effect of the intronic variant on splicing, but the tool SpliceRover was successful in detecting a cryptic exon. Further RNA sequencing confirmed the presence of the cryptic exon. The patient exhibited typical symptoms of TCTN2-related disorders along with some uncommon features. These findings highlight the usefulness of genome sequencing and RNA sequencing in molecular diagnosis and suggest the potential of SpliceRover in extracting candidate variants from intronic variants in genome sequencing.
JOURNAL OF HUMAN GENETICS
(2023)
Letter
Endocrinology & Metabolism
Makiko Yano, Takeshi Sato, Satsuki Nakano, Sachiko Shimozato, Tomohiro Ishii, Tomonobu Hasegawa
JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM
(2023)
Review
Biochemistry & Molecular Biology
Atsushi Hattori, Maki Fukami
Summary: This review article discusses the relationship between pathogenic variants of three nuclear receptor genes (NR5A1, NR0B1, and NR2F2) and disorders of sex development (DSD). NR5A1 variants are associated with 46,XY DSD and 46,XX testicular/ovotesticular DSD. NR0B1 and NR2F2 mutations are also implicated in DSD, but their exact roles are still unclear. Understanding these nuclear receptors provides new insights into the molecular networks involved in human fetal gonadal development.
Article
Genetics & Heredity
Hazuki Morikawa, Sachiko Nishina, Kaoruko Torii, Katsuhiro Hosono, Tadashi Yokoi, Chika Shigeyasu, Masakazu Yamada, Motomichi Kosuga, Maki Fukami, Hirotomo Saitsu, Noriyuki Azuma, Yuichi Hori, Yoshihiro Hotta
Summary: We present the case of a 1-year-old girl with congenital stromal corneal dystrophy confirmed by genetic analysis. The patient exhibited bilateral diffuse opacity over the corneal stroma. Genetic analysis using whole exome sequencing identified a novel de novo variant, NM_001920.5: c.953del, p.(Asn318Thrfs*10), in the DCN gene. This information is important for counseling the parents regarding the recurrence risk.
HUMAN GENOME VARIATION
(2023)
Article
Endocrinology & Metabolism
Naoko Amano, Satoshi Narumi, Katsuya Aizu, Mari Miyazawa, Kohji Okamura, Hirofumi Ohashi, Noriyuki Katsumata, Tomohiro Ishii, Tomonobu Hasegawa
Summary: This study aimed to explore a new genetic form of primary adrenal insufficiency (PAI). Through analysis of nine childhood-onset patients with biochemically and genetically unknown PAI, various-sized single-exon deletions involving ZNRF3 exon 2 were identified. Further research showed that these deletions could lead to the inactivation of RSPO1-dependent Wnt/β-catenin signaling.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Review
Obstetrics & Gynecology
Erina Suzuki, Mami Miyado, Yoko Kuroki, Maki Fukami
Summary: The human hypothalamic-pituitary-gonadal (HPG) axis regulates pubertal development and involves six G-protein coupled receptors (GPCRs). Rare variants of these GPCR genes have been identified in patients with pubertal disorders. Loss-of-function variants in KISS1R, TACR3, PROKR2, and GNRHR cause hypogonadotropic hypogonadism, while gain-of-function variants of KISS1R, PROKR2, and LHCGR are implicated in precocious puberty. More research is needed to fully understand the molecular network involving these GPCRs.
REPRODUCTIVE MEDICINE AND BIOLOGY
(2023)
Article
Endocrinology & Metabolism
Chisato Narita, Noriyuki Takubo, Manami Sammori, Yuko Matsumura, Kazuhiro Shimura, Rie Ozaki, Hidenori Haruna, Satoshi Narumi, Tomohiro Ishii, Tomonobu Hasegawa, Toshiaki Shimizu
Summary: This article reports a case of 46,XY complete gonadal dysgenesis with a novel missense variant in the SRY gene, which was diagnosed after primary amenorrhea. The patient underwent surgery and genetic analysis to confirm the diagnosis, and continued with hormone replacement therapy.
CLINICAL PEDIATRIC ENDOCRINOLOGY
(2023)