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
Genetics & Heredity
Margot A. Cousin, Blake A. Creighton, Keith A. Breau, Rebecca C. Spillmann, Erin Torti, Sruthi Dontu, Swarnendu Tripathi, Deepa Ajit, Reginald J. Edwards, Simone Afriyie, Julia C. Bay, Kathryn M. Harper, Alvaro A. Beltran, Lorena J. Munoz, Liset Falcon Rodriguez, Michael C. Stankewich, Richard E. Person, Yue Si, Elizabeth A. Normand, Amy Blevins, Alison S. May, Louise Bier, Vimla Aggarwal, Grazia M. S. Mancini, Marjon A. van Slegtenhorst, Kirsten Cremer, Jessica Becker, Hartmut Engels, Stefan Aretz, Jennifer J. MacKenzie, Eva Brilstra, Koen L. I. van Gassen, Richard H. van Jaarsveld, Renske Oegema, Gretchen M. Parsons, Paul Mark, Ingo Helbig, Sarah E. McKeown, Robert Stratton, Benjamin Cogne, Bertrand Isidor, Pilar Cacheiro, Damian Smedley, Helen V. Firth, Tatjana Bierhals, Katja Kloth, Deike Weiss, Cecilia Fairley, Joseph T. Shieh, Amy Kritzer, Parul Jayakar, Evangeline Kurtz-Nelson, Raphael A. Bernier, Tianyun Wang, Evan E. Eichler, Ingrid M. B. H. van de Laar, Allyn McConkie-Rosell, Marie T. McDonald, Jennifer Kemppainen, Brendan C. Lanpher, Laura E. Schultz-Rogers, Lauren B. Gunderson, Pavel N. Pichurin, Grace Yoon, Michael Zech, Robert Jech, Juliane Winkelmann, Adriana S. Beltran, Michael T. Zimmermann, Brenda Temple, Sheryl S. Moy, Eric W. Klee, Queenie K. -G. Tan, Damaris N. Lorenzo
Summary: SPTBN1 mutations cause a neurodevelopmental syndrome with intellectual disability, language and motor delays, and other features. Heterozygous SPTBN1 variants disrupt beta II-spectrin stability, binding to molecular partners, and disturb cytoskeleton organization and dynamics, suggesting compromise of neural development and function. This study expands the understanding of spectrinopathies affecting the brain and highlights the critical role of beta II-spectrin in the central nervous system.
Article
Urology & Nephrology
Veronica Arora, Suliman Khan, Ayman W. El-Hattab, Ratna Dua Puri, Maria Eugenia Rocha, Rijad Merdzanic, Omid Paknia, Christian Beetz, Arndt Rolfs, Aida M. Bertoli-Avella, Peter Bauer, Ishwar C. Verma
Summary: A study identified the causal role of GFRA1 gene variants in bilateral renal agenesis, potentially manifesting as an autosomal recessive, nonsyndromic form. This finding will facilitate early genetic diagnosis and improved genetic counseling for families at risk of BRA.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Genetics & Heredity
Guillaume Olivier, Marta Corton, Daniela Intartaglia, Sanne K. Verbakel, Panagiotis Sergouniotis, Guylene Le Meur, Claire-Marie Dhaenens, Helene Naacke, Almudena Avila-Fernandez, Carel B. Hoyng, Jeroen Klevering, Beatrice Bocquet, Agathe Roubertie, Audrey Senechal, Sandro Banfi, Agnes Muller, Christian L. Hamel, Graeme C. Black, Ivan Conte, Susanne Roosing, Xavier Zanlonghi, Carmen Ayuso, Isabelle Meunier, Gael Manes
Summary: This study reveals a previously unreported association between monoallelic or biallelic IMPG1 variants and RP, as well as the identification of new genetic variants associated with this gene. The clinical diagnosis of the IMPG1 retinopathy-associated variant has been revised from benign concentric annular macular dystrophy to RP with early macular involvement.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Le Guo, Bob P. H. Engelen, Irene M. G. M. Hemel, Irenaeus F. M. de Coo, Maaike Vreeburg, Suzanne C. E. H. Sallevelt, Debby M. E. Hellebrekers, Ed H. Jacobs, Farah Sadeghi-Niaraki, Florence H. J. van Tienen, Hubert J. M. Smeets, Mike Gerards
Summary: In a Dutch patient with non-consanguineous mitochondrial encephalomyopathy, two compound heterozygous variants in SLIRP were found through whole exome sequencing. Experimental results showed that the SLIRP variants led to reduced mitochondrial mass and impaired OXPHOS activity in patient fibroblasts. Restoration of wild-type SLIRP expression partly recovered OXPHOS activity, confirming the causality of the variants.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Genetics & Heredity
Joanna Kulikowska, Anna Jakubiuk-Tomaszuk, Malgorzata Rydzanicz, Rafal Ploski, Jan Kochanowicz, Alina Kulakowska, Katarzyna Kapica-Topczewska
Summary: This paper presents a case of a 53-year-old Caucasian female patient with rare variants in the ERCC4 gene, which are associated with several autosomal recessive diseases. The patient exhibited various symptoms including movement disorders, speech problems, memory deterioration, and skin pigmentation. Genetic analysis confirmed two variants in the ERCC4 gene. This case highlights the occurrence of rare genetic causes of progressive neurodegenerative diseases in adults.
FRONTIERS IN GENETICS
(2023)
Article
Medical Laboratory Technology
Miaohua Ruan, Hongwei Wang, Mianmian Zhu, Rongyue Sun, Jiamin Shi, Qiu Wang, Yuan Chen, Yihong Wang, Dan Wang
Summary: This study identified novel compound heterozygous variants of the CWF19L1 gene in a Chinese family with progressive ataxia and mental retardation of unknown etiology. These variants may be a novel cause of recessive ataxia with developmental delay. Whole-exome sequencing was efficient in screening disease-associated variants, providing potential for novel therapies and enriching the variant spectrum of the CWF19L1 gene for future studies on genotype-phenotype correlations.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2022)
Article
Genetics & Heredity
Christina Votsi, Antonis Ververis, Paschalis Nicolaou, Yiolanda-Panayiota Christou, Kyproula Christodoulou, Eleni Zamba-Papanicolaou
Summary: This study reports a large Cypriot family with spastic ataxia caused by a novel homozygous missense variant in the SPG7 gene. The patients exhibited typical features of spastic ataxia, but phenotypic variation was observed within the family. Functional studies revealed aberrant mitochondrial morphology, indicating the pathogenicity of the identified variant.
FRONTIERS IN GENETICS
(2022)
Article
Biology
Bryn D. Webb, Sara M. Nowinski, Ashley Solmonson, Jaya Ganesh, Richard J. Rodenburg, Joao Leandro, Anthony Evans, Hieu S. Vu, Thomas P. Naidich, Bruce D. Gelb, Ralph J. DeBerardinis, Jared Rutter, Sander M. Houten
Summary: In this study, we reported a patient with pathogenic variants in MCAT, presenting with hypotonia, failure to thrive, nystagmus, and abnormal brain MRI findings. Biallelic variants in MCAT were identified through whole exome sequencing. Protein levels of subunits of complex I and IV, NDUFB8 and COXII respectively, were significantly reduced in lymphoblasts and fibroblasts, as well as SDHB for complex II in fibroblasts. ETC enzyme activities were decreased accordingly. Re-expression of wild-type MCAT rescued the phenotype in patient fibroblasts. This is the first report of a patient with MCAT pathogenic variants and combined oxidative phosphorylation deficiency.
Article
Genetics & Heredity
Francesca Mattioli, Lina Worpenberg, Cai-Tao Li, Nazia Ibrahim, Shagufta Naz, Saima Sharif, Saghar G. Firouzabadi, Shohreh Vosoogh, Radoslava Saraeva-Lamri, Laure Raymond, Carlos Trujillo, Nicolas Guex, Stylianos E. Antonarakis, Muhammad Ansar, Hossein Darvish, Ru-Juan Liu, Jean-Yves Roignant, Alexandre Reymond
Summary: By combining exome sequencing and functional characterization, we identified NSUN6 as a new neurodevelopmental disorder gene, with its mutations leading to intellectual disability.
GENETICS IN MEDICINE
(2023)
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)
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)
Article
Cell Biology
Alicia B. Byrne, Pascal Brouillard, Drew L. Sutton, Jan Kazenwadel, Saba Montazaribarforoushi, Genevieve A. Secker, Anna Oszmiana, Milena Babic, Kelly L. Betterman, Peter J. Brautigan, Melissa White, Sandra G. Piltz, Paul Q. Thomas, Christopher N. Hahn, Matthias Rath, Ute Felbor, G. Christoph Korenke, Christopher L. Smith, Kathleen H. Wood, Sarah E. Sheppard, Denise M. Adams, Ariana Kariminejad, Raphael Helaers, Laurence M. Boon, Nicole Revencu, Lynette Moore, Christopher Barnett, Eric Haan, Peer Arts, Miikka Vikkula, Hamish S. Scott, Natasha L. Harvey
Summary: Central conducting lymphatic anomaly (CCLA) is a severe disorder of the lymphatic system often resulting in fetal or perinatal demise. This study identified pathogenic variants in the MDFIC gene in individuals with CCLA and revealed a crucial role for MDFIC in lymphatic vessel development.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Genetics & Heredity
Ken Saida, Junya Tamaoki, Masayuki Sasaki, Muzhirah Haniffa, Eriko Koshimizu, Toru Sengoku, Hiroki Maeda, Masahiro Kikuchi, Haruna Yokoyama, Masamune Sakamoto, Kazuhiro Iwama, Futoshi Sekiguchi, Kohei Hamanaka, Atsushi Fujita, Takeshi Mizuguchi, Kazuhiro Ogata, Noriko Miyake, Satoko Miyatake, Makoto Kobayashi, Naomichi Matsumoto
Summary: Cerebellar ataxia is a genetically heterogeneous disorder caused by biallelic loss-of-function variants in the GEMIN5 gene, leading to neurodevelopmental delay, hypotonia, and cerebellar atrophy/hypoplasia. Zebrafish models further confirmed the pathogenicity of these variants.
Article
Genetics & Heredity
Daniel L. Polla, Mohammad Ali Farazi Fard, Zahra Tabatabaei, Parham Habibzadeh, Olga A. Levchenko, Pooneh Nikuei, Periklis Makrythanasis, Mureed Hussain, Sandra von Hardenberg, Sirous Zeinali, Mohammad-Sadegh Fallah, Janneke H. M. Schuurs-Hoeijmakers, Mohsin Shahzad, Fareeha Fatima, Neelam Fatima, Laura Donker Kaat, Hennie T. Bruggenwirth, Leah R. Fleming, John Condie, Rafal Ploski, Agnieszka Pollak, Jacek Pilch, Nina A. Demina, Alena L. Chukhrova, Vasilina S. Sergeeva, Hanka Venselaar, Amira T. Masri, Hanan Hamamy, Federico A. Santoni, Katrin Linda, Zubair M. Ahmed, Nael Nadif Kasri, Arjan P. M. de Brouwer, Anke K. Bergmann, Sven Hethey, Majid Yavarian, Muhammad Ansar, Saima Riazuddin, Sheikh Riazuddin, Mohammad Silawi, Gaia Ruggeri, Filomena Pirozzi, Ebrahim Eftekhar, Afsaneh Taghipour Sheshdeh, Shima Bahramjahan, Ghayda M. Mirzaa, Alexander V. Lavrov, Stylianos E. Antonarakis, Mohammad Ali Faghihi, Hans van Bokhoven
Summary: The study identified biallelic variants in the TMEM222 gene as a novel underlying cause of an autosomal recessive neurodevelopmental disorder in 17 individuals from nine unrelated families. Further investigation revealed relatively high levels of TMEM222 expression in the human brain, particularly in the parietal and occipital cortex, with subcellular localization analysis showing TMEM222 localizing to early endosomes in synapses of mature neurons.
GENETICS IN MEDICINE
(2021)
Review
Endocrinology & Metabolism
Minela Haskovic, Ana I. Coelho, Jorgen Bierau, Jo M. Vanoevelen, Laura K. M. Steinbusch, Luc J. I. Zimmermann, Eduardo Villamor-Martinez, Gerard T. Berry, M. Estela Rubio-Gozalbo
JOURNAL OF INHERITED METABOLIC DISEASE
(2020)
Article
Endocrinology & Metabolism
Minela Haskovic, Ana I. Coelho, Martijn Lindhout, Fokje Zijlstra, Raisa Veizaj, Rein Vos, Jo M. Vanoevelen, Jorgen Bierau, Dirk J. Lefeber, M. Estela Rubio-Gozalbo
JOURNAL OF INHERITED METABOLIC DISEASE
(2020)
Article
Cell Biology
Auke B. C. Otten, Rick Kamps, Patrick Lindsey, Mike Gerards, Helene Pendeville-Samain, Marc Muller, Florence H. J. van Tienen, Hubert J. M. Smeets
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
Article
Multidisciplinary Sciences
Dimitrios Kapsokalyvas, Rodrigo Rosas, Rob W. A. Janssen, Jo M. Vanoevelen, Miranda Nabben, Martin Strauch, Dorit Merhof, Marc A. M. J. van Zandvoort
Summary: The study successfully applied the Multiview microscopy technique to achieve Multiview imaging with multiphoton microscopy, achieving isotropic resolution and suppressing interference artifacts, which is significant for clear visualization of collagen fibrils and myofibrils.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Le Guo, Bob P. H. Engelen, Irene M. G. M. Hemel, Irenaeus F. M. de Coo, Maaike Vreeburg, Suzanne C. E. H. Sallevelt, Debby M. E. Hellebrekers, Ed H. Jacobs, Farah Sadeghi-Niaraki, Florence H. J. van Tienen, Hubert J. M. Smeets, Mike Gerards
Summary: In a Dutch patient with non-consanguineous mitochondrial encephalomyopathy, two compound heterozygous variants in SLIRP were found through whole exome sequencing. Experimental results showed that the SLIRP variants led to reduced mitochondrial mass and impaired OXPHOS activity in patient fibroblasts. Restoration of wild-type SLIRP expression partly recovered OXPHOS activity, confirming the causality of the variants.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Pharmacology & Pharmacy
Roel R. I. van Reij, Maud M. A. Salmans, Ivo Eijkenboom, Nynke J. van den Hoogen, Elbert A. J. Joosten, Jo M. Vanoevelen
Summary: The study investigated the role of dopamine in nociception and analgesia, demonstrating the importance of dopamine receptor drd2a in anti-nociceptive behavior in zebrafish. The findings suggest potential for further research on genetic variations and treatments related to nociception.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Cell Biology
Irene M. G. M. Hemel, Bob P. H. Engelen, Nicole Luber, Mike Gerards
Summary: The study analyzed five open source ImageJ tools and found that the Mitochondrial Analyzer outperforms other tools in accurate identification and structural segregation of mitochondria, making it the best open source tool for mitochondrial network morphology quantification.
Article
Clinical Neurology
Le Guo, Periyasamy Govindaraj, Marielle Kievit, Irenaeus F. M. de Coo, Mike Gerards, Debby M. E. I. Hellebrekers, Alphons P. M. Stassen, Narayanappa Gayathri, Arun B. Taly, Bindu Parayil Sankaran, Hubert J. M. Smeets
Summary: Whole exome sequencing identified a homozygous deletion in the C1QBP gene in a patient with late-onset PEO-plus syndrome without cardiac involvement. Mutations in C1QBP can result in different clinical presentations, with early-onset cardiomyopathy variants affecting important structural domains and PEO-plus variants involving the coiled-coil region.
NEUROMUSCULAR DISORDERS
(2021)
Article
Clinical Neurology
Jo M. Vanoevelen, Jorgen Bierau, Janine C. Grashorn, Ellen Lambrichs, Erik-Jan Kamsteeg, Levinus A. Bok, Ron A. Wevers, Marjo S. van der Knaap, Marianna Bugiani, Junmei Hu Frisk, Rita Colnaghi, Mark O'Driscoll, Debby M. E. Hellebrekers, Richard Rodenburg, Carlos R. Ferreira, Han G. Brunner, Arthur van den Wijngaard, Ghada M. H. Abdel-Salam, Liya Wang, Constance T. R. M. Stumpel
Summary: The study reveals that impairing the biosynthesis of dTTP, a crucial DNA building block, leads to early-onset neurodegenerative disease characterized by severe microcephaly and growth retardation. Microcephaly, neuronal cell death, and early lethality were replicated in dtymk mutant zebrafish models. Furthermore, increased ribonucleotide incorporation in the genome and impaired responses to DNA damage were observed in these mutant zebrafish, providing novel insights into the pathophysiology of the disease. The loss-of-function of DTYMK was identified as the cause of this severe postnatal neurodegenerative disease, emphasizing the essential role of dTTP synthesis in maintaining genome stability and neuronal survival.
ACTA NEUROPATHOLOGICA
(2022)
Article
Biochemistry & Molecular Biology
Irene M. G. M. Hemel, Rita Sarantidou, Mike Gerards
Summary: Mitochondria undergo changes in shape, size, and number in response to cellular demand through mitochondrial dynamics. The interaction between mitochondria and ER, especially at ER-mitochondrial contact sites, plays a crucial role in regulating mitochondrial dynamics. Various protein complexes tether mitochondria to the ER, influencing processes like fission, fusion, and calcium homeostasis that impact mitochondrial dynamics.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Junmei Hu Frisk, Jo M. Vanoevelen, Jorgen Bierau, Gunnar Pejler, Staffan Eriksson, Liya Wang
Summary: Mutations in deoxythymidylate kinase (TMPK) lead to loss of function, but patient-derived cells still grow normally, indicating the presence of an unknown compensatory TMPK-like enzyme. Further studies will help elucidate the role of TMPK in neuropathology.
Article
Endocrinology & Metabolism
Britt Delnoy, Minela Haskovic, Jo Vanoevelen, Laura K. M. Steinbusch, Esther Naomi Vos, Kevin Knoops, Luc J. Zimmermann, Marek Noga, Dirk J. Lefeber, Paolo G. Martini, Ana Coelho, Maria Estela Rubio-Gozalbo
Summary: This study investigates the potential of human GALT mRNA therapy for classic galactosemia using a zebrafish model. The results demonstrate that mRNA injections can restore GALT protein and enzyme activity, while reducing the accumulation of metabolites caused by the deficiency.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Review
Genetics & Heredity
Irenaeus F. M. de Coo, Sarah Jesse, Thuy-Linh Le, Carlo Sala
Summary: Phelan-McDermid syndrome (PMS) is a 22q13.3 deletion syndrome characterized by developmental disturbances, neurological and psychiatric features, and sometimes comorbidities such as seizures. Different types of seizures can occur in PMS and the use of EEG and MRI is important for diagnosis and determining the need for anticonvulsant therapy. This study focused on the prevalence and semiology of epileptic seizures associated with the SHANK3 gene or 22q13 deletion involving SHANK3 in PMS, in order to provide recommendations for diagnosis and therapy as part of European consensus guidelines.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2023)
Article
Cardiac & Cardiovascular Systems
Rachel M. A. ter Bekke, Koen de Schouwer, Sergio Conti, Godelieve R. F. Claes, Jo Vanoevelen, Suzanne Gommers, Apollonia T. J. M. Helderman-van den Enden, Hans-Peter Brunner-LaRocca
Summary: This study reports a case of a 16-year-old patient presenting with atrial brady- and tachyarrhythmias and subsequent development of atrial standstill and AV dilated cardiomyopathy. Genetic analysis revealed missense mutation and copy number variant deletion of the TAF1A gene associated with ribosomal RNA synthesis. This highlights the importance of genetic research in cases of juvenile atrial electromechanical failure and the need for vigilance in monitoring for cardiomyopathic deterioration.
EUROPEAN HEART JOURNAL-CASE REPORTS
(2023)
Article
Clinical Neurology
Roy A. M. Haast, Irenaeus F. M. De Coo, Dimo Ivanov, Ali R. Khan, Jacobus F. A. Jansen, Hubert J. M. Smeets, Kamil Uludag
Summary: In this study, the researchers used high-resolution MRI data to identify neurodegenerative and functional changes in the cerebellum of m.3243A > G patients. The results showed altered tissue integrity and reduced functional connectivity in specific regions of the cerebellar cortex. This study provides valuable insights into the neuropathological changes associated with the m.3243A > G mutation.
BRAIN COMMUNICATIONS
(2022)