Article
Clinical Neurology
Bedia Samanci, Ebru Erzurumluoglu Gokalp, Basar Bilgic, Hakan Gurvit, Sevilhan Artan, Hasmet A. Hanagasi
Summary: Loss-of-function mutations in the sacsin gene can cause autosomal recessive spastic ataxia, such as seen in the Turkish ARSACS family presented here. Whole gene sequencing was advantageous in detecting novel mutations in this case, where the patient exhibited progressive spastic ataxia and dysarthria.
NEUROLOGICAL SCIENCES
(2021)
Article
Medicine, General & Internal
Izumi Aida, Tetsuo Ozawa, Hidehiko Fujinaka, Kiyoe Goto, Kentaro Ohta, Takashi Nakajima
Summary: ARSACS is a rare progressive neurodegenerative disease caused by mutations in the SACS gene, with diverse phenotypes observed in different regions and ethnic groups. While original cases were largely found in Quebec, atypical cases have been identified in other populations as well.
Review
Biochemistry & Molecular Biology
Jaya Bagaria, Eva Bagyinszky, Seong Soo A. An
Summary: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease that was originally discovered in Quebec. It is characterized by spasticity and ataxia, with retinal optic nerve hypermyelination being a common feature. Over 200 mutations in the SACS gene have been identified worldwide.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
William Beauchesne, Florence Ouellet-Dupuis, Marc-Antoine Frigon, Catherine Savard, Valerie Gagne-Ouellet, Cynthia Gagnon, Karine Tremblay
Summary: The aim of this study was to characterize the profile of cannabis use among patients with ARSACS. Among the 50 study participants, 18% currently used cannabis, 40% reported at least one occurrence of cannabis use, and 42% reported having never used cannabis. A greater proportion of patients with regular cannabis use reported chronic pain in comparison to those who never used.
JOURNAL OF CLINICAL NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Khaled A. Aly, Mohamed Taha Moutaoufik, Mara Zilocchi, Sadhna Phanse, Mohan Babu
Summary: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare early-onset neurodegenerative disease caused by mutations in the SACS gene. Understanding the function of Sacsin and using ARSACS disease models can improve our knowledge of this disease. Gene correction strategies and delivery methods provide hope for the development of therapeutics for ARSACS.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
Article
Clinical Neurology
Flavio Moura Rezende Filho, Fion Bremner, Jose Luiz Pedroso, Joao Brainer Clares de Andrade, Bruna Ferraco Marianelli, Charles Marques Lourenco, Wilson Marques-Junior, Marcondes C. Franca, Fernando Kok, Juliana M. F. Sallum, Michael H. Parkinson, Orlando G. Barsottini, Paola Giunti
Summary: This study investigated retinal abnormalities in patients with ARSACS and found highly specific abnormalities suggesting retinal hyperplasia due to abnormal retinal development. Optical coherence tomography (OCT) may provide potential biomarkers for future clinical trials.
MOVEMENT DISORDERS
(2021)
Editorial Material
Radiology, Nuclear Medicine & Medical Imaging
Rosmi Hassan Karuvath, Sriram Patwari, Harsha Chadaga
Summary: The 6-year-old male child presented with a history of ataxia and delayed motor development, with no family history of neurodegenerative disease. Examination showed abnormal neurologic functions, and electromyography revealed predominantly sensory axonal neuropathy. Unenhanced MRI of the brain was performed upon arrival, with selected images presented.
Article
Materials Science, Multidisciplinary
Ozlem Sen, Melis Emanet, Attilio Marino, Melike Belenli Gumus, Martina Bartolucci, Stefano Doccini, Federico Catalano, Giada Graziana Genchi, Filippo Maria Santorelli, Andrea Petretto, Gianni Ciofani
Summary: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurological disease with no effective therapies proposed. Resveratrol-loaded nanostructured lipid carriers (Res-NLCs) show promising therapeutic potential for ARSACS treatment, encouraging further pre-clinical investigations.
MATERIALS & DESIGN
(2021)
Article
Neurosciences
Mahmoud Reza Ashrafi, Pouria Mohammadi, Ali Reza Tavasoli, Morteza Heidari, Sareh Hosseinpour, Maryam Rasulinejad, Mohammad Rohani, Masoud Ghahvechi Akbari, Reza Azizi Malamiri, Reza Shervin Badv, Davood Fathi, Ali Zare Dehnavi, Shahram Savad, Ali Rabbani, Matthis Synofzik, Nejat Mahdieh, Zahra Rezaei
Summary: Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) is one of the most common autosomal recessive ataxias, characterized by progressive cerebellar ataxia, spasticity, and sensorimotor polyneuropathy. However, not all patients exhibit the classic clinical triad. Brain magnetic resonance imaging (MRI) shows symmetric linear hypointensities in the pons and anterior superior cerebellar atrophy, as well as a hyperintense rim around the thalami. This study expands the molecular spectrum of ARSACS, identifying new genetic variants and reporting anterior temporal arachnoid cyst as a potential associated imaging feature.
Article
Neurosciences
Brenda Toscano Marquez, Anna A. Cook, Max Rice, Alexia Smileski, Kristen Vieira-Lomasney, Francois Charron, R. Anne McKinney, Alanna J. Watt
Summary: Patterned cell death is evident in neurodegenerative diseases like ARSACS, with vulnerable Purkinje cells linked to specific molecular patterns. Understanding the molecular and spatial factors influencing cell death can provide insights into disease mechanisms.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Zhanjun Wang, Yang Song, Xianling Wang, Xuying Li, Fanxi Xu, Lianghao Si, Yue Dong, Tingyan Yao, Junge Zhu, Hong Lai, Wei Li, Feng Lin, Huapin Huang, Chaodong Wang
Summary: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare hereditary disease caused by mutations in the SACS gene, which encodes the sacsin protein. Two Chinese ARSACS patients with novel mutations were identified through whole-exome sequencing (WES). The mutations were predicted to be loss-of-function affecting important C-terminal domains, providing new insights into the mutational and clinical spectrum of ARSACS.
NEUROSCIENCE LETTERS
(2021)
Article
Genetics & Heredity
Marjolaine Tremblay, Laura Girard-Cote, Bernard Brais, Cynthia Gagnon
Summary: This study aimed to understand the manifestations and impacts of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Through a systematic review and qualitative study, the results revealed physical, mental, and social aspects of the disease. The physical symptoms mentioned by participants were fatigue, balance issues, and dexterity struggles, while mental health impacts included frustration, depression, and cognitive abilities loss. Social relationships, activities, and work were significantly affected as well.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Genetics & Heredity
Qaiser Zaman, Muhammad Abbas Khan, Kalsoom Sahar, Gauhar Rehman, Hamza Khan, Mehwish Rehman, Najumuddin, Ilyas Ahmad, Muhmmad Tariq, Osama Yousef Muthaffar, Angham Abdulrhman Abdulkareem, Fehmida Bibi, Muhammad Imran Naseer, Muhammad Shah Faisal, Naveed Wasif, Musharraf Jelani
Summary: This study reported rare cases of MPV17, SACS, PRX, and GJB1 gene mutations causing Charcot-Marie-Tooth disease and spastic ataxia of Charlevoix-Saguenay type in the Pakistani population. Whole exome sequencing was found to be a useful tool in diagnosing complex multigenic and phenotypically overlapping genetic disorders such as CMT and ARSACS.
Editorial Material
Clinical Neurology
Jenny L. L. Hepschke, Yusuf Ali Rajabally, Susan P. P. Mollan
Summary: This case report describes the optic nerve features of a 23-year-old male patient diagnosed with autosomal recessive spastic ataxia of Charlevoix-Saguenay.
Article
Neurosciences
Isabelle Lessard, Isabelle Cote, Raphael St-Gelais, Luc J. Hebert, Bernard Brais, Jean Mathieu, Xavier Rodrigue, Cynthia Gagnon
Summary: This study aimed to document the natural history of ARSACS over a 4-year period, and found that severe balance and walking capacity impairments were present, with a significant performance decrease over time. The study also revealed rapid progression rates in upper limb coordination, pinch strength, balance, and walking capacity in the ARSACS population. These findings are crucial for informing patients, developing specific rehabilitation programs, and improving trial readiness.
Article
Genetics & Heredity
Jessica Omark, Yohei Masunaga, Mark Hannibal, Brandon Shaw, Maki Fukami, Fumiko Kato, Hirotomo Saitsu, Masayo Kagami, Tsutomu Ogata
Summary: This study reported a case of an African American female infant with Kagami-Ogata syndrome (KOS14) phenotype caused by a chromosomal translocation involving the 14q32.2 imprinted region. The analysis revealed disruption of MEG3 leading to excessive RTL1 expression as a potential mechanism for KOS14 development.
JOURNAL OF HUMAN GENETICS
(2021)
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
Genetics & Heredity
Sachiko Miyamoto, Mitsuko Nakashima, Shinobu Fukumura, Satoko Kumada, Hirotomo Saitsu
Summary: This study reported an intronic variant in the GNAO1 gene, which was found to cause abnormal splicing and result in the insertion of 2 amino acids, leading to movement disorders. By conducting RNA testing and immunological methods, the researchers found that the cellular localization pattern of the mutant protein was different from the wild type.
Article
Genetics & Heredity
Yohei Masunaga, Yumiko Ohkubo, Gen Nishimura, Taizo Ueno, Yasuko Fujisawa, Maki Fukami, Hirotomo Saitsu, Tsutomu Ogata
Summary: This study reports a case of a Japanese girl with severe idiopathic short stature caused by biallelic loss-of-function variants in the ACAN gene. The findings provide new evidence for the association between ACAN gene mutations and idiopathic short stature.
JOURNAL OF HUMAN GENETICS
(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
Kazuki Watanabe, Mitsuko Nakashima, Rie Wakatsuki, Tomoyasu Bunai, Yasuomi Ouchi, Tomohiko Nakamura, Hiroaki Miyajima, Hirotomo Saitsu
Summary: This study investigated the genetic basis and brain metabolism and blood flow of a Japanese family with spinocerebellar degeneration (SCD). Whole-exome sequencing (WES) and whole-genome sequencing (WGS) were performed, but no likely pathogenic variants were identified. ExpansionHunter Denovo detected repeat expansions in the RFC1 gene, leading to the diagnosis of RFC1-related disorders. The patients showed a variety of clinical features, including motor neuropathy and cognitive impairment. Imaging studies revealed cortical damage in some patients, while others showed no apparent cerebral damage.
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
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)