Article
Clinical Neurology
Haiping Wang, Xiuli Chen, Zhanli Liu, Chen Chen, Xin Liu, Mingwei Huang, Zhuying Zhou
Summary: STXBP1 variants are a common genetic cause of neurodevelopmental disorders and epilepsy. However, there is a wide spectrum of genotype and phenotype with no clear correlations established. This study reports a new STXBP1 splice variant and provides detailed documentation of disease manifestations and treatment. Further investigation of STXBP1 splice variants and functional studies are needed for a better understanding of the genotype-phenotype relationship.
FRONTIERS IN NEUROLOGY
(2023)
Article
Cell Biology
Kathy N. Lam, Peter Spanogiannopoulos, Paola Soto-Perez, Margaret Alexander, Matthew J. Nalley, Jordan E. Bisanz, Renuka R. Nayak, Allison M. Weakley, Feiqiao B. Yu, Peter J. Turnbaugh
Summary: The study demonstrates the use of engineered bacteriophage M13 to deliver DNA to Escherichia coli in the mouse gastrointestinal tract, enabling strain-specific depletion and genomic deletions. Multiple mechanisms allow E. coli to escape targeting, providing a foundation for microbiome editing and suggesting potential for extension to other phage-bacterial pairs.
Article
Biochemistry & Molecular Biology
Ji-Hye Oh, Sungyang Jo, Kye Won Park, Eun-Jae Lee, Seung Hyun Lee, Yun Su Hwang, Ha Ra Jeon, Yeonjin Ryu, Hee Jeong Yoon, Sung-Min Chun, Chong Jai Kim, Tae Won Kim, Chang Ohk Sung, Sehyun Chae, Sun Ju Chung
Summary: A whole-genome sequencing study of Korean individuals with Parkinson's disease (PD) has identified several new genetic risk factors, ranging from single nucleotide variations (SNVs) to larger DNA deletions. These findings provide a global, whole-genome view of PD and suggest that small genomic deletions in regulatory domains contribute to the risk of PD development.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2023)
Article
Genetics & Heredity
Maria Tofilo, Natalia Voronova, Leila Nigmatullina, Elena Kuznetsova, Valeria Timonina, Bogdan Efimenko, Oybek Turgunkhujaev, Svetlana Avdeichik, Muhammad Ansar, Konstantin Popadin, Anastasia Kirillova, Ilya Mazunin
Summary: We reported a rare metabolic disorder called molybdenum cofactor deficiency type B (MOCODB), which has been observed in only 37 affected patients. A homozygous variant in the MOCS2 gene was found in an affected child, who was diagnosed with Ohtahara syndrome. Preimplantation genetic testing for monogenic disorders (PGT-M) was used to select embryos without the MOCS2 gene mutation in an in vitro fertilization program, resulting in the birth of a healthy child. Interestingly, both parents shared the same mitochondrial DNA control region, suggesting a possible close maternal relationship and the transmission of the rare MOCS2 gene variant from a common female ancestor.
Article
Cell & Tissue Engineering
Chunmei Wang, Yilin Wang, Wuhen Xu, Xuefeng Lin, Jiaming Xi, Simei Wang, Longlong Lin, Fang Yuan, Anqi Wang, Chao Wang, Xiaona Luo, Quanmei Xu, Rongrong Yin, Yuanfeng Zhang, Xiaoyi Huang, Yucai Chen
Summary: This study reports a patient with ARX-related disorders exhibiting intellectual disability, early-onset epileptic encephalopathy, and Ohtahara syndrome. The patient had female genitals, but an XY karyotype. The researchers established an iPSC line from PBMCs and demonstrated its normal differentiation potential.
STEM CELL RESEARCH
(2022)
Article
Clinical Neurology
Hanna Mierzewska, Milena Laure-Kamionowska, Aleksandra Jezela-Stanek, Malgorzata Rydzanicz, Rafal Ploski, Elzbieta Szczepanik
Summary: Developmental and epileptic encephalopathies (DEE) are severe and drug-resistant disorders starting in the first year of life, with DEE43 caused by dominant mutations in the GABRB3 gene. The neuropathological analysis revealed various developmental anomalies and retardation of myelination in a novel case, highlighting the importance of understanding the pathomechanism of the disease for effective treatment.
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
(2021)
Article
Oncology
Lin Dong, Shuangmei Zou, Xianglan Jin, Haizhen Lu, Ye Zhang, Lei Guo, Jianqiang Cai, Jianming Ying
Summary: This study identified rare cytoplasmic MSH2 staining in CRC patients, some of whom had LS with pathogenic mutations in MSH2 and/or EPCAM, including large genomic rearrangements. Analysis revealed novel RNA fusions and deletions of EPCAM and MSH2, originating from Alu repeat-mediated recombination events. Clinical evidence supported the beneficial effect of PD-1 inhibitor pembrolizumab in CRC patients with cytoplasmic MSH2 staining.
FRONTIERS IN ONCOLOGY
(2021)
Review
Pediatrics
Gregorio Serra, Vincenzo Antona, Mario Giuffre, Ettore Piro, Sergio Salerno, Ingrid Anne Mandy Schierz, Giovanni Corsello
Summary: Interstitial deletions of the short arm of chromosome 1 are rare and can lead to a variety of clinical features, including global developmental delay, dysmorphic face, ocular defects, and cleft palate.
ITALIAN JOURNAL OF PEDIATRICS
(2022)
Article
Oncology
Anna Eriksson, Marie Engvall, Lucy Mathot, Albin Osterroos, Martin Rippin, Lucia Cavelier, Claes Ladenvall, Panagiotis Baliakas
Summary: In this study, it was found that somatic RUNX1 exonic deletions are a recurrent aberration in AML, and that RUNX1 mutations can be acquired during the development of the disease. The presence of RUNX1 aberrations has important implications for AML classification, risk stratification, and treatment decisions. Furthermore, these findings highlight the need for further investigation into similar genomic aberrations in other genes involved in cancer biology and management.
CLINICAL CANCER RESEARCH
(2023)
Review
Genetics & Heredity
Elena-Silvia Shelby, Michael Morris, Liliana Padure, Andrada Mirea, Relu Cocos, Alexandru Caramizaru, Simona Serban-Sosoi, Andrei Pirvu, Ioana Streata
Summary: 19q13 microdeletion syndrome is a rare genetic disease characterized by growth retardation and intellectual disability. This article reports the first case of this syndrome in Romania, with some unique features not previously reported.
Article
Agriculture, Dairy & Animal Science
Kunpeng Liu, Ao Qi, Wenxiu Ru, Xiaojun Jiang, Hui Cao, Xianyong Lan, Yongzhen Huang, Chuzhao Lei, Xiuzhu Sun, Hong Chen
Summary: This study identified two Indels within the bovine FoxO1 gene in Chinese adult cows and found that these Indels could be used as genetic markers for marker-assisted selection in cattle breeding.
ANIMAL BIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Tom van der Valk, Marianne Dehasque, J. Camilo Chacon-Duque, Nikolay Oskolkov, Sergey Vartanyan, Peter D. Heintzman, Patricia Pecnerova, David Diez-del-Molino, Love Dalen
Summary: Woolly mammoths had genetic adaptations, including deletions and indels, that contributed to their unique phenotypic adaptations for surviving in the Arctic environment.
Article
Multidisciplinary Sciences
Haipo Yang, Pan Gong, Xianru Jiao, Qiujun Zhou, Yuehua Zhang, Yuwu Jiang, Zhixian Yang
Summary: The study found that patients with genetic epilepsy were more likely to exhibit asynchronous and symmetric BS patterns, while those with structural epilepsies were more likely to have synchronous and asymmetric BS patterns.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, General & Internal
Xi Zhou, Jingjing Wang, Jianhua Mao, Qing Ye
Summary: Alport syndrome-diffuse leiomyomatosis is a rare type of X-linked Alport syndrome caused by deletions in the COL4A6 gene. Female patients tend to have milder symptoms, lower rates of proteinuria and ocular abnormalities, and are less likely to develop sensorineural hearing loss or chronic kidney disease compared to male patients. The pathogenesis of the characteristic deletion of COL4A6 that contributes to diffuse leiomyomatosis remains unknown. Additionally, the contiguous deletion of COL4A5 and COL4A6 genes in AS-DL may be related to transposed elements (TEs).
FRONTIERS IN MEDICINE
(2021)
Article
Oncology
James M. Cleary, Srivatsan Raghavan, Qibiao Wu, Yvonne Y. Li, Liam F. Spurr, Hersh Gupta, Douglas A. Rubinson, Isobel J. Fetter, Jason L. Hornick, Jonathan A. Nowak, Giulia Siravegna, Lipika Goyal, Lei Shi, Lauren K. Brais, Maureen Loftus, Atul B. Shinagare, Thomas A. Abrams, Thomas E. Clancy, Jiping Wang, Anuj K. Patel, Franck Brichory, Anne Vaslin Chessex, Ryan J. Sullivan, Rachel B. Keller, Sarah Denning, Emma R. Hill, Geoffrey Shapiro, Anna Pokorska-Bocci, Claudio Zanna, Kimmie Ng, Deborah Schrag, Pasi A. Janne, William C. Hahn, Andrew D. Cherniack, Ryan B. Corcoran, Matthew Meyerson, Antoine Daina, Vincent Zoete, Nabeel Bardeesy, Brian M. Wolpin
Summary: FGFR2 EIDs are shown to be an alternative mechanism of FGFR2 activation in intrahepatic cholangiocarcinoma (IHCC), predicting sensitivity to FGFR inhibitors and treatment benefits in patients with these alterations.
Article
Genetics & Heredity
Takuya Hiraide, Yohei Masunaga, Akira Honda, Fumiko Kato, Tokiko Fukuda, Maki Fukami, Mitsuko Nakashima, Hirotomo Saitsu, Tsutomu Ogata
Summary: This article describes X-linked dominant chondrodysplasia punctata (CDPX2), a rare congenital disorder, and identifies the presence of retrotransposition-induced insertion in the genes of two patients through whole genome sequencing.
JOURNAL OF HUMAN GENETICS
(2022)
Article
Genetics & Heredity
Takuya Hiraide, Kenji Shimizu, Sachiko Miyamoto, Kazushi Aoto, Mitsuko Nakashima, Tomomi Yamaguchi, Tomoki Kosho, Tsutomu Ogata, Hirotomo Saitsu
Summary: Exome sequencing and panel testing have improved the diagnostic yield in genetic analysis. This study utilized genome sequencing and RNA sequencing to explore the genetic basis of Marfan syndrome in a family. The findings suggest that urinary cells can be used as a clinically accessible tissue for RNA sequencing, especially when disease-causing genes are poorly expressed in the blood.
JOURNAL OF HUMAN GENETICS
(2022)
Article
Clinical Neurology
Mitsuhiro Kato, Akiko Kada, Hideaki Shiraishi, Jun Tohyama, Eiji Nakagawa, Yukitoshi Takahashi, Tomoyuki Akiyama, Akiyoshi Kakita, Noriko Miyake, Atsushi Fujita, Akiko M. Saito, Yushi Inoue
Summary: Sirolimus has a certain inhibitory effect on focal seizures in patients with FCD type II, however, the reduction level did not reach statistical significance.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Genetics & Heredity
Kazuo Abe, Kumiko Ando, Mitsuhiro Kato, Hirotomo Saitsu, Mitsuko Nakashima, Shintaro Aoki, Takashi Kimura
Summary: This study reports a case of a 24-year-old male patient with intellectual disability and childhood-onset seizures. The patient was found to have newly identified biallelic variants in the LAMC3 gene, along with previously unreported cortical malformations. The findings suggest a unique role of LAMC3 in brain development.
NEUROLOGY-GENETICS
(2022)
Article
Genetics & Heredity
Takuya Hiraide, Tenpei Akita, Kenji Uematsu, Sachiko Miyamoto, Mitsuko Nakashima, Masayuki Sasaki, Atsuo Fukuda, Mitsuhiro Kato, Hirotomo Saitsu
Summary: This study reports a case of KCNB1 mutation that results in a milder phenotype compared to previously reported cases. The brain MRI of the patient showed characteristic abnormalities, and functional analysis revealed that the mutant variant reduces channel activation and inactivation at specific membrane voltages.
JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Mitsuko Nakashima, Emanuela Argilli, Sayaka Nakano, Elliott H. Sherr, Mitsuhiro Kato, Hirotomo Saitsu
Summary: A recent study discovered that genetic variants in the CLCN3 gene can cause neurodevelopmental disorders and brain abnormalities. The study found that some variants had a gain-of-function effect on channel activity. Two patients with specific CLCN3 variants showed severe neurological symptoms and a range of brain abnormalities. These findings expand our understanding of CLCN3-related disorders.
JOURNAL OF HUMAN GENETICS
(2023)
Article
Clinical Neurology
Kaoru Yamamoto, Shimpei Baba, Takashi Saito, Eiji Nakagawa, Kenji Sugai, Masaki Iwasaki, Atsushi Fujita, Hiromi Fukuda, Takeshi Mizuguchi, Mitsuhiro Kato, Naomichi Matsumoto, Masayuki Sasaki
Summary: Suppression-burst (SB) is an EEG pattern observed in DEEs, which are associated with high mortality in early life. This study investigated the relation between SB-EEG and autonomic function in DEEs to explore the mechanism of early death. The results showed that patients with KCNT1-DEE exhibited synchronous HR fluctuations during SB-EEG, with a decrease in HR during suppression and an increase during burst. Patients with KCNT1-DEE had larger HR decreases and longer suppression durations compared to other patients. A strong negative correlation was found between suppression duration and HR reduction rates in one patient with KCNT1-DEE.
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)
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
Genetics & Heredity
Kazuki Watanabe, Kazuo Kubota, Mitsuko Nakashima, Hirotomo Saitsu
Summary: This study presents a unique case of a patient with typical NF1 findings and infantile spasms who had three potentially pathogenic de novo variants in NF1 and one variant in GABBR1. It contributes to our understanding of the impact of these variants on NF1 phenotypes and GABBR1-related neuropsychiatric disorders.
HUMAN GENOME VARIATION
(2023)
Article
Genetics & Heredity
Karin Kojima, Takahito Wada, Hiroko Shimbo, Takahiro Ikeda, Eriko F. Jimbo, Hirotomo Saitsu, Naomichi Matsumoto, Takanori Yamagata
Summary: The ATRX variant c.21-1G>A was detected in a patient with Cockayne syndrome without ATR-XS. This variant leads to abnormal splicing and results in a slightly shorter but functional ATRX protein.
HUMAN GENOME VARIATION
(2022)
Article
Genetics & Heredity
Marina Hashiguchi, Yukifumi Monden, Yasuyuki Nozaki, Kazuki Watanabe, Mitsuko Nakashima, Hirotomo Saitsu, Takanori Yamagata, Hitoshi Osaka
Summary: TUBB4A gene variants can cause dystonia type 4 and hypomyelination with atrophy of the basal ganglia and cerebellum. This case report highlights the vulnerability of the cerebellum in patients with TUBB4A pathogenic variants.
HUMAN GENOME VARIATION
(2022)
Article
Genetics & Heredity
Shogo Furukawa, Sachiko Miyamoto, Shinobu Fukumura, Kazuo Kubota, Toshiaki Taga, Mitsuko Nakashima, Hirotomo Saitsu
Summary: Variants in ATP1A3 play a significant role in neuropsychiatric disorders, particularly those characterized by movement disorders. Whole exome sequencing identified two novel ATP1A3 variants in two patients with movement disorders, including a missense variant and an indel variant.
HUMAN GENOME VARIATION
(2022)
