Article
Cell Biology
Deepa S. Rajan, Sukhleen Kour, Tyler R. Fortuna, Margot A. Cousin, Sarah S. Barnett, Zhiyv Niu, Dusica Babovic-Vuksanovic, Eric W. Klee, Brian Kirmse, Micheil Innes, Siri Lynne Rydning, Kaja K. Selmer, Magnus Dehli Vigeland, Anne Kjersti Erichsen, Andrea H. Nemeth, Francisca Millan, Catherine DeVile, Katherine Fawcett, Adrien Legendre, David Sims, Ricardo Parolin Schnekenberg, Lydie Burglen, Sandra Mercier, Somayeh Bakhtiari, Encarnacion Martinez-Salas, Kristen Wigby, Jerica Lenberg, Jennifer R. Friedman, Michael C. Kruer, Udai Bhan Pandey
Summary: This study discovered biallelic variants in the GEMIN5 gene among nine affected individuals, leading to abnormal protein structure and reduced expression of snRNP complex proteins. The research expands on the phenotypic spectrum associated with GEMIN5-related disease, providing insights into patients with spastic ataxia, cerebellar atrophy, and motor predominant developmental delay.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Clinical Neurology
Han-Lin Chiang, Jong-Ling Fuh, Yu-Shuen Tsai, Bing-Wen Soong, Yi-Chu Liao, Yi-Chung Lee
Summary: Mutations in the AFG3L2 gene can cause a broad spectrum of diseases, including SCA28 and SPAX5. This study identified a patient with compound heterozygous mutations in AFG3L2, expanding the clinical spectrum and suggesting a new subtype of late-onset SCAR.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2021)
Article
Genetics & Heredity
Haseena Sait, Amita Moirangthem, Vinita Agrawal, Shubha R. Phadke
Summary: Autosomal recessive spinocerebellar ataxia-20 is a rare disorder characterized by distinctive coarse facies, intellectual disability, and cerebellar ataxia, caused by biallelic variants in the SNX14 gene. This study reports a novel case with confirmed pathogenic variants in SNX14 gene through genetic sequencing and expression analysis. Electron microscopy of skin fibroblasts revealed abnormal cytoplasmic vacuoles, providing further insights into the cellular pathology of the disease.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Review
Clinical Neurology
Giulia Coarelli, Marie Coutelier, Alexandra Durr
Summary: Dominantly inherited spinocerebellar ataxias (SCAs) exhibit phenotypic variation and can be caused by multiple potentially pathogenic variants. Genome sequencing should be the preferred diagnostic tool due to the extreme clinical and genetic heterogeneity, but its availability is limited. Although treatments like riluzole and transcranial direct current stimulation have been tested, their efficacy remains conflicting. Biomarkers, such as neurofilament light chain and brain MRI, should be used to assess preataxic carriers and monitor target engagement by gene therapies.
Article
Genetics & Heredity
Kari J. Ekenstedt, Katie M. Minor, G. Diane Shelton, James J. Hammond, Andrew D. Miller, Susan M. Taylor, Yanyun Huang, James R. Mickelson
Summary: ARSACS is a human neurological disorder characterized by progressive cerebellar ataxia and peripheral neuropathy. A similar disorder was recently identified in Great Pyrenees dogs, showing widespread central nervous system degeneration leading to progressive cerebellar ataxia and spasticity, combined with peripheral neuropathy. The disease follows an autosomal recessive inheritance pattern and is associated with mutations in the SACS gene.
Article
Clinical Neurology
Natasa Dragasevic-Miskovic, Iva Stankovic, Andona Milovanovic, Vladimir S. Kostic
Summary: Autosomal recessive ataxias (ARCA) encompass a wide range of diseases, from primary ataxias to complex metabolic disorders where ataxia is just one aspect. Proper differential diagnosis is crucial for adult-onset ARCA, as they may be treatable and have prognostic implications.
JOURNAL OF NEUROLOGY
(2022)
Review
Clinical Neurology
Marie Beaudin, Mario Manto, Jeremy D. Schmahmann, Massimo Pandolfo, Nicolas Dupre
Summary: In this Review, the authors discuss recessive ataxias with ganglionopathy or polyneuropathy, focusing on Friedreich ataxia and RFC1-associated cerebellar ataxia, neuropathy, vestibular areflexia syndrome. They explore the shared pathogenic mechanisms and therapeutic advances in these diseases. The Review also provides insights into the diagnostic challenges and clinical features of these diseases.
NATURE REVIEWS NEUROLOGY
(2022)
Article
Genetics & Heredity
Nannan Qian, Taohua Wei, Wenming Yang, Jiuxiang Wang, Shijie Zhang, Shan Jin, Wei Dong, Wenjie Hao, Yue Yang, Ru Huang
Summary: ARCA-1 (or SCAR8) is a hereditary cerebellar ataxia caused by SYNE1 gene mutation. Its clinical features are primarily characterized by cerebellar ataxia and may be accompanied by upper and/or lower motor neuron dysfunction.
FRONTIERS IN GENETICS
(2022)
Review
Clinical Neurology
Andreas Traschuetz, Selina Reich, Astrid D. Adarmes, Mathieu Anheim, Mahmoud Reza Ashrafi, Jonathan Baets, A. Nazli Basak, Enrico Bertini, Bernard Brais, Cynthia Gagnon, Janina Gburek-Augustat, Hasmet A. Hanagasi, Anna Heinzmann, Rita Horvath, Peter de Jonghe, Christoph Kamm, Peter Klivenyi, Thomas Klopstock, Martina Minnerop, Alexander Muenchau, Mathilde Renaud, Richard H. Roxburgh, Filippo M. Santorelli, Tommaso Schirinzi, Deborah A. Sival, Dagmar Timmann, Stefan Vielhaber, Michael Wallner, Bart P. van de Warrenburg, Ginevra Zanni, Stephan Zuchner, Thomas Klockgether, Rebecca Schuele, Ludger Schols, Matthis Synofzik
Summary: ARCAs form a rare group of neurodegenerative diseases, the ARCA Registry is a global multicenter platform aiming to advance trial readiness for ARCAs, providing GCP- and GDPR-compliant professional-reported registry with modular eCRFs for data capture tailored to different site interests and resources.
FRONTIERS IN NEUROLOGY
(2021)
Article
Neurosciences
Xia Liu, Wei Lin, Lin Zhang, Wan-Li Zhang, Xiao-Ping Cheng, Yan-Hua Lian, Meng-Cheng Li, Shi-Zhong Wang, Xin-Yuan Chen, Shi-Rui Gan
Summary: This study aims to investigate the effects of transcranial alternating current stimulation (tACS) on patients with cerebellar ataxia (CA) and assess its safety. A total of 164 CA patients will be selected and randomly assigned to receive either active tACS or sham treatment. The results will provide insights into a potential novel non-invasive therapeutic approach for CA patients.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Neurosciences
Ping- Chiang, Ting-Wei Liao, Chiung-Mei Chen
Summary: This study reports the first case of AOA2/SCAN2 in Taiwan, identified through next-generation sequencing. The study found that ataxia, polyneuropathy, and elevated alpha-fetoprotein are common features of AOA2, while ocular motor apraxia varies among different populations.
Article
Clinical Neurology
Min-Yu Lan, Chin-Song Lu, Shey-Lin Wu, Ying-Fa Chen, Yueh-Feng Sung, Min-Chien Tu, Yung-Yee Chang
Summary: This study characterized the clinical and genetic features of HSP patients with concurrent cerebellar ataxia and identified causative mutations in multiple genes. The study revealed the genetic complexity and functional overlap in HSP with cerebellar involvement.
FRONTIERS IN NEUROLOGY
(2022)
Review
Genetics & Heredity
Ashraf Yahia, Giovanni Stevanin
Summary: Hereditary spinocerebellar degeneration (SCD) comprises a group of rare diseases with diverse clinical and genetic characteristics, making diagnosis and management challenging. Precision medicine relies on accurate diagnosis, and discovering genes causing unknown conditions can guide patient and family management and lead to the identification of more genetic diseases.
FRONTIERS IN GENETICS
(2021)
Review
Chemistry, Medicinal
Sze Yuen Lew, Michael Weng Lok Phang, Pit Shan Chong, Jaydeep Roy, Chi Him Poon, Wing Shan Yu, Lee Wei Lim, Kah Hui Wong
Summary: This systematic review evaluates the current developments in therapeutic strategies targeting oxidative stress for the management of autosomal recessive cerebellar ataxias (ARCAs). The review finds that antioxidant therapies show promise in improving or halting the progression of the disease. Tailoring the therapies to specific disease stages could greatly facilitate disease management.
Article
Clinical Neurology
Sara Radmard, Theresa A. Zesiewicz, Sheng-Han Kuo
Summary: The hallmarks of cerebellar ataxia are incoordination and movement variability. The cerebellum not only controls motor coordination but also plays a role in cognition and mood. Determining the underlying cause of cerebellar ataxia is necessary, and the causes are extensive, requiring laboratory studies and imaging for systematic workup. Genetic testing often leads to a specific cause for cerebellar ataxia, and acquired and reversible causes should be pursued for disease-modifying treatment. Rapid expansion in the field of cerebellar ataxia is bringing hope with actively tested new therapies.
NEUROLOGIC CLINICS
(2023)
Article
Genetics & Heredity
Smrithi Salian, Xin-Yu Guo, Yoshiko Murakami, Taroh Kinoshita, Parneet Kaur, Anju Shukla, Katta M. Girisha, Morihisa Fujita, Philippe M. Campeau
Summary: We identified a pathogenic variant in the C18orf32 gene as the cause of a novel autosomal recessive neurodevelopmental disorder. Our study demonstrates the importance of C18orf32 in GPI-anchor biosynthesis, the functional and localization abnormalities of the mutant C18orf32 protein.
Letter
Genetics & Heredity
Mangalore S. Shravya, Mary Mathew, Akhila Vasudeva, Katta M. Girisha, Shalini S. Nayak
Review
Genetics & Heredity
Benjamin D. Solomon, Margaret P. Adam, Chin-To Fong, Katta M. Girisha, Judith G. Hall, Anna C. E. Hurst, Peter M. Krawitz, Shahida Moosa, Shubha R. Phadke, Cedrik Tekendo-Ngongang, Tara L. Wenger
Summary: The field of clinical genetics and genomics is evolving with milestones like the sequencing of the human genome, advances in sequencing technologies, and the introduction of artificial intelligence. The practice of dysmorphology, the study of abnormal development of tissue form, has also been influenced by technological advances and trends in biomedicine. To explore the future of dysmorphology, a group of clinical geneticists have provided insights about its development over the next few decades.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Shalini S. Nayak, Robert Harkness, Anju Shukla, Siddharth Banka, William G. Newman, Katta M. Girisha
Summary: Urorectal septum malformation sequence (URSMS) is a spectrum of anomalies involving the urogenital system, hindgut, and perineum. This study analyzed 12 cases of URSMS in fetuses and found that it often coexists with malformations in other systems.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Letter
Genetics & Heredity
Sheela Nampoothiri, Jeanne Maria Dsouza, Dhanya Yesodharan, Katta M. Girisha, Malini Eapen, Sajitha Sivasankaran Nair, Bhanu Vikraman Pillai, Periyasamy Radhakrishnan
Article
Biochemistry & Molecular Biology
Debasish Kumar Ghosh, Prajna Udupa, Akshaykumar Nanaji Shrikondawar, Gandham SriLakshmi Bhavani, Hitesh Shah, Akash Ranjan, Katta M. Girisha
Summary: Aberrant forms of endoplasmic reticulum (ER)-resident chaperones are associated with protein quality control loss in rare diseases. A novel mutation (p.Asp233Asn) in the ER localization signal of MESD was identified in a patient with osteogenesis imperfecta (OI) type XX using whole exome sequencing. The mutant MESDD233N mislocalizes to the cytoplasm, disrupting ER proteostasis and leading to improper folding and aggregation of proteins, including LRP5 and type I collagen. Consequently, there is impaired WNT signaling and cytosolic accumulation of type I collagen aggregates, affecting cell-matrix interactions and cellular stress response.
Article
Genetics & Heredity
Shruti Pande, Selinda Mascarenhas, Aishwarya Venkatraman, Vivekananda Bhat, Dhanya Lakshmi Narayanan, Shahyan Siddiqui, Stephanie Bielas, Katta Mohan Girisha, Anju Shukla
Summary: Heterozygous disease-causing variants in BCL11B are responsible for a rare neurodevelopmental syndrome involving craniofacial and immunological abnormalities. We report three new cases with de novo heterozygous frameshift variants in exon 4 of BCL11B, all presenting with developmental delay, recurrent infections, facial dysmorphism, and variable degrees of craniosynostosis. This study expands the knowledge of genotypes and phenotypes associated with BCL11B-related BAFopathy and provides insights into the clinical and genomic spectrum of this disorder.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Sheila Unger, Carlos R. R. Ferreira, Geert R. R. Mortier, Houda Ali, Debora R. Bertola, Alistair Calder, Daniel H. H. Cohn, Valerie Cormier-Daire, Katta M. M. Girisha, Christine Hall, Deborah Krakow, Outi Makitie, Stefan Mundlos, Gen Nishimura, Stephen P. P. Robertson, Ravi Savarirayan, David Sillence, Marleen Simon, V. Reid Sutton, Matthew L. L. Warman, Andrea Superti-Furga
Summary: The classification of genetic skeletal disorders has been revised in its 11th edition, now including 771 entries associated with 552 genes, reflecting advancements in DNA sequencing technology. The adoption of the dyadic naming system is the most notable change, systematically linking a phenotypic entity to the gene it originates from. This shift is considered a significant improvement, providing more informative and error-resistant nomenclature compared to traditional methods. Despite the adoption of dyadic naming, efforts have been made to maintain a strong connection to the MIM catalog and its historical data. The list of disorders and genes in the Nosology remains valuable for differential diagnosis, bioinformatic analysis, and driving advancements in biology and medicine.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Review
Genetics & Heredity
Charles W. Ryan, Emily R. Peirent, Samantha L. Regan, Alba Guxholli, Stephanie L. Bielas
Summary: Metazoan development depends on the spatiotemporal control of gene expression, which is regulated by epigenetic regulators called polycomb group proteins (PcG). PcG proteins control gene expression, cell fate decisions, cell cycle progression, and DNA damage repair by adding or removing histone 2A monoubiquitination at lysine 119 (H2AK119ub1). Dysfunction of PcG genes is associated with developmental disorders, as their pathogenic variants disrupt essential developmental mechanisms. This review discusses the clinical manifestations of pathogenic PcG gene variants, their molecular functions during development, and summarizes the current understanding of the genetic and molecular mechanisms.
Article
Genetics & Heredity
Subrahmanya Vasishta, Akkatai S. Teli, Akhila Vasudeva, Katta M. Girisha, Shalini S. Nayak
Summary: Cardiospondylocarpofacial syndrome is a rare condition caused by monoallelic variants in the MAP3K7 gene. It is characterized by growth retardation, facial dysmorphism, carpal-tarsal fusion, dorsal spine synostosis, deafness, inner ear malformation, cardiac septal defect and valve dysplasia. We report a 20-week-old fetus with prenatal manifestation of cardiospondylocarpofacial syndrome, arising from a de novo variant in the MAP3K7 gene. This is the first report mentioning the prenatal manifestation of this syndrome.
PRENATAL DIAGNOSIS
(2023)
Article
Genetics & Heredity
Swati Singh, Prince Jacob, Siddaramappa J. Patil, Mamta Muranjan, Hitesh Shah, Katta M. Girisha, Gandham SriLakshmi Bhavani
Summary: This study delineates the clinical presentation of nine individuals with CHST3-related chondrodysplasia with congenital joint dislocations and suggests monitoring the health of cardiac valves in this condition.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Biochemistry & Molecular Biology
Prajna Udupa, Akshaykumar Nanaji Shrikondawar, Shalini S. Nayak, Hitesh Shah, Akash Ranjan, Katta M. Girisha, Gandham SriLakshmi Bhavani, Debasish Kumar Ghosh
Summary: By sequencing the genome of a male fetus with osteogenesis imperfecta (OI) type VII, this study identifies a deep intronic variant, c.794_1403A>G, in the CRTAP gene, which introduces cryptic splice sites and generates mutant isoforms of the protein. These mutant isoforms are unstable due to a unique degradation signal, resulting in loss of proline hydroxylation and aggregation of type I collagen, leading to cell senescence and death.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Review
Oncology
Neha Quadri, Priyanka Upadhyai
Summary: Primary cilia play a fundamental role in vertebrate cells, modulating organismal development, morphogenesis, and repair. This article focuses on their involvement in skeletal development, examining evidence of their role in signaling pathways and their relevance to skeletal disorders. The authors discuss the molecular factors and mechanisms governing primary ciliogenesis and ciliary function in skeletal development and disease.
EXPERIMENTAL CELL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Almundher Al-Maawali, Fathiya Al-Murshedi, Amna Al-Futaisi, Ahmed Mansy, Asila Al-Habsi, Katta M. Girisha
Summary: Biallelic loss of function variants in SV2A result in early onset intractable epilepsy, with affected children being normal at birth but developing recurrent seizures beginning in the second month of life and experiencing secondary failure of growth and development.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)