Article
Clinical Neurology
Sophia Caldas Gonzaga da Costa, Flavio e de Rezende-Filho, Julian Leticia de Freitas, Paula Camila Alves de Assis Pereira Matos, Bruno Della-Ripa, Marcondes Cavalcante Franca, Wilson Marques, Mariana Santos, Igor Vasconcelos Barros Cronemberger, Thiago Cardoso Vale, Fernando Kok, Isabel Alonso, Jose Luiz Pedroso, Orlando G. P. Barsottini
Summary: Through genetic investigation, it was found that AOA2 and AOA4 were the most common subtypes of autosomal recessive cerebellar ataxia plus oculomotor apraxia in Brazil. Pathogenic variants in SETX, PNKP, and APTX genes were frequently identified, while mutations in PIK3R5 and XRCC1 were less common.
MOVEMENT DISORDERS
(2022)
Article
Clinical Neurology
Xuan Wu, Nan Dong, Zhensheng Liu, Tieyu Tang, Meirong Liu
Summary: Ataxia with oculomotor apraxia type 1 (AOA1) is a rare genetic disorder characterized by childhood-onset progressive cerebellar ataxia. This study reports the first genetically confirmed patient of AOA1 in a Chinese family and identifies a novel APTX gene mutation.
FRONTIERS IN NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Radhakrishnan Kanagaraj, Richard Mitter, Theodoros Kantidakis, Matthew M. Edwards, Anaid Benitez, Probir Chakravarty, Beiyuan Fu, Olivier Becherel, Fengtang Yang, Martin F. Lavin, Amnon Koren, Aengus Stewart, Stephen C. West
Summary: Mutations in the SETX gene are associated with progressive neurodegenerative diseases AOA2 and ALS4. Genomic and transcriptomic analysis of patient-derived cells and SETX knockout models revealed an increase in chromosomal instability, changes in gene-expression profiles, and the role of transcription stress in SETX mutationassociated chromosome fragility and AOA2.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Andrology
Christian Corsini, Giuseppe Fallara, Luigi Candela, Massimiliano Raffo, Edoardo Pozzi, Federico Belladelli, Paolo Capogrosso, Luca Boeri, Antonio Costa, Nicolo Schifano, Daniele Cignoli, Eugenio Ventimiglia, Alessia D'Arma, Francesco Montorsi, Andrea Salonia
Summary: The study found that higher serum AFP levels are associated with abnormal sperm counts, older age, obesity, and a greater amount of comorbid conditions in males seeking medical attention for couple's primary infertility.
Article
Genetics & Heredity
Praseetha Kizhakkedath, Watfa AlDhaheri, Ibrahim Baydoun, Mohammed Tabouni, Anne John, Taleb M. Almansoori, Saeed Al-Turki, Fatma Al-Jasmi, Hiba Alblooshi
Summary: BILAPES is an autosomal recessive cerebro-renal syndrome caused by genetic defects in the SLC30A9 gene. It was initially reported in a large Bedouin kindred and has only been described in a few patients. In this study, two additional patients from a consanguineous Middle Eastern family were reported, showing consistent features with BILAPES. Whole-exome sequencing identified a homozygous in-frame deletion in the SLC30A9 gene, which was the same variant detected in the previous patients. However, the patients in this study showed cerebellar atrophy, which was not observed in the previous reports.
FRONTIERS IN GENETICS
(2023)
Review
Gastroenterology & Hepatology
Dana A. Dominguez, Paul Wong, Laleh G. Melstrom
Summary: This review discusses the lack of sensitive and specific biomarkers for predicting prognosis, monitoring minimal residual disease, and predicting treatment response in hepatocellular carcinoma (HCC). Although alpha-fetoprotein (AFP) is the most widely used biomarker, its applicability is limited. Liquid biopsy provides potential biomarkers, but validation in large clinical trials is lacking. Clinical trials are critical for the development of optimal therapeutic regimens and improvement of patient outcomes.
HEPATOBILIARY SURGERY AND NUTRITION
(2023)
Review
Medicine, Research & Experimental
Raidah Albaradie, Alanoud Alharbi, Gada Alsaffar, Bayader Alhamad, Shahid Bashir
Summary: This study reported the clinical features of an 8-year-old female patient with ataxia with oculomotor apraxia type 1 (AOA1) caused by mutations in the APTX gene, and discussed the differential diagnosis from other forms of hereditary ataxia.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2022)
Article
Immunology
Stefan Zielen, Ruth Pia Duecker, Sandra Woelke, Helena Donath, Sharhzad Bakhtiar, Aileen Buecker, Hermann Kreyenberg, Sabine Huenecke, Peter Bader, Nizar Mahlaoui, Stephan Ehl, Sabine M. El-Helou, Barbara Pietrucha, Alessandro Plebani, Michiel van der Flier, Koen van Aerde, Sara S. Kilic, Shereen M. Reda, Larysa Kostyuchenko, Elizabeth McDermott, Nermeen Galal, Claudio Pignata, Juan Luis Santos Perez, Hans-Juergen Laws, Tim Niehues, Necil Kutukculer, Markus G. Seidel, Laura Marques, Peter Ciznar, John David M. Edgar, Pere Soler-Palacin, Horst von Bernuth, Renate Krueger, Isabelle Meyts, Ulrich Baumann, Maria Kanariou, Bodo Grimbacher, Fabian Hauck, Dagmar Graf, Luis Ignacio Gonzalez Granado, Seraina Prader, Ismail Reisli, Mary Slatter, Carlos Rodriguez-Gallego, Peter D. Arkwright, Claire Bethune, Elena Deripapa, Svetlana O. Sharapova, Kai Lehmberg, E. Graham Davies, Catharina Schuetz, Gerhard Kindle, Ralf Schubert
Summary: The study analyzed mortality and immunity data of patients with ataxia-telangiectasia (A-T) in relation to IgA deficiency, finding that patients with IgA deficiency have significantly lower survival rates, lymphocyte counts, and subsets compared to A-T patients without IgA deficiency. This suggests that IgA deficiency may indicate a poorer prognosis for classical A-T patients.
JOURNAL OF CLINICAL IMMUNOLOGY
(2021)
Article
Biology
Huiping Wang, Wensha Nie, Chunxia Wang, Zuohua Wang, Yuxia Zheng
Summary: This study analyzed the characteristics of clinical phenotypes and CPLANE1 variants in a 2-month-old JBTS patient. The patient presented with oculomotor apraxia, dysregulation of breathing pattern, and ataxia, and a novel CPLANE1 variant was discovered.
OPEN LIFE SCIENCES
(2023)
Article
Clinical Neurology
Karan K. Topiwala, Smit D. Patel, Mubashir Pervez, Claire L. Shovlin, Mark J. Alberts
Summary: Pulmonary arteriovenous fistulas (PAVFs) are a treatable cause of acute ischemic stroke, possibly related to hereditary hemorrhagic telangiectasia. Patients with PAVF are younger, have lower inpatient morbidity and case fatality rates, and exhibit several independent risk markers for AIS.
Article
Genetics & Heredity
Troels Hvelplund, Bibi Lange, Susanne Djernes Bird, Malene Korsholm, Anette Drohse Kjeldsen
Summary: This study evaluated the implementation of five outcome measures recommended by the European Reference Network for Rare Vascular Diseases in HHT patients. The study found that the target thresholds were achieved for screening PAVM and assessing iron deficiency. However, the target thresholds for providing written advice on nosebleed, antibiotic prophylaxis, and pregnancy were not achieved.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Medicine, General & Internal
Freya Droege, Andreas Stang, Kruthika Thangavelu, Carolin Lueb, Stephan Lang, Michael Xydakis, Urban Geisthoff
Summary: The study revealed a higher prevalence of restless leg syndrome (RLS) in patients with hereditary hemorrhagic telangiectasia (HHT), with some cases going undiagnosed. Patients with HHT who had a history of gastrointestinal bleeding, blood transfusions, or iron intake were more likely to have RLS. This suggests that RLS may be underdiagnosed in HHT patients and highlights the importance of assessing iron deficiency anemia parameters.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Penina Ponger, Alina Kurolap, Israela Lerer, Judith Dagan, Chofit Chai Gadot, Adi Mory, Yael Wilnai, Nino Oniashvili, Nir Giladi, Tanya Gurevich, Vardiella Meiner, Alexander Lossos, Hagit Baris Feldman
Summary: This study reports new clinical features of AOA2 and provides in-depth analysis of its genetic variations. The study found that novel in-frame deletion and duplication variants in the SETX gene can affect DNA repair and RNA maturation, leading to the onset of the disease. In addition, the study also discovered a previously undescribed poison exon in the SETX gene, which may contribute to the development of tailored therapy.
JOURNAL OF MOLECULAR NEUROSCIENCE
(2022)
Article
Public, Environmental & Occupational Health
Hatice Saracoglu, Mevlut Baskol, Hakan Saracoglu, Gulden Baskol
Summary: Alpha-fetoprotein (AFP) is a tumor biomarker expressed by tumors with a high mitotic index. Elevated AFP levels without underlying causes can indicate a rare benign condition called hereditary persistence of AFP (HPAFP). We report the first case of HPAFP from Turkey with higher AFP levels than previously reported cases.
MALAWI MEDICAL JOURNAL
(2022)
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
Endocrinology & Metabolism
Pippa Staps, William B. Rizzo, Frederic M. Vaz, Marianna Bugiani, Martin Giera, Bram Heijs, Antoine H. C. van Kampen, Mia L. Pras-Raves, Marjolein Breur, Annemieke Groen, Sacha Ferdinandusse, Marinette van der Graaf, Gert Van Goethem, Martin Lammens, Ron A. Wevers, Michel A. A. P. Willemsen
JOURNAL OF INHERITED METABOLIC DISEASE
(2020)
Article
Genetics & Heredity
Flora Szeri, Stefan Lundkvist, Sylvia Donnelly, Udo F. H. Engelke, Kyu Rhee, Charlene J. Williams, John P. Sundberg, Ron A. Wevers, Ryan E. Tomlinson, Robert S. Jansen, Koen van de Wetering
Article
Genetics & Heredity
Emma J. Graham Linck, Phillip A. Richmond, Maja Tarailo-Graovac, Udo Engelke, Leo A. J. Kluijtmans, Karlien L. M. Coene, Ron A. Wevers, Wyeth Wasserman, Clara D. M. van Karnebeek, Sara Mostafavi
NPJ GENOMIC MEDICINE
(2020)
Article
Genetics & Heredity
Daisy Rymen, Martijn Lindhout, Maria Spanou, Farah Ashrafzadeh, Ira Benkel, Cornelia Betzler, Christine Coubes, Hans Hartmann, Julie D. Kaplan, Diana Ballhausen, Johannes Koch, Jan Lotte, Mohammad Hasan Mohammadi, Marianne Rohrbach, Argirios Dinopoulos, Marieke Wermuth, Daniel Willis, Karin Brugger, Ron A. Wevers, Eugen Boltshauser, Jorgen Bierau, Johannes A. Mayr, Saskia B. Wortmann
GENETICS IN MEDICINE
(2020)
Review
Endocrinology & Metabolism
Tessa Wassenberg, Jaap Deinum, Frans J. van Ittersum, Erik-Jan Kamsteeg, Maartje Pennings, Marcel M. Verbeek, Ron A. Wevers, Mirjam E. van Albada, Ido P. Kema, Jorie Versmissen, Ton van den Meiracker, Jacques W. M. Lenders, Leo Monnens, Michel A. Willemsen
Summary: DBH deficiency is a rare genetic disorder characterized by severe orthostatic hypotension, which can be treated with L-DOPS. Patients show significant improvement with L-DOPS treatment, but orthostatic hypotension, renal function, anemia, and hypomagnesemia remain partially resolved.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Roel Tans, Rieke Bande, Arno van Rooij, Billy J. Molloy, Rinke Stienstra, Cees J. Tack, Ron A. Wevers, Hans J. C. T. Wessels, Jolein Gloerich, Alain J. van Gool
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
(2020)
Article
Neurosciences
Anouke van Rumund, Lukas Pavelka, Rianne A. J. Esselink, Ben P. M. Geurtz, Ron A. Wevers, Brit Mollenhauer, Rejko Krueger, Bastiaan R. Bloem, Marcel M. Verbeek
Summary: The study found that Parkinson's disease patients using peripheral decarboxylase inhibitors had elevated serum AADC enzyme activity, which may lead to the need for increased levodopa dosage to maintain therapeutic effects.
NPJ PARKINSONS DISEASE
(2021)
Article
Biology
Rianne E. van Outersterp, Sam J. Moons, Udo F. H. Engelke, Herman Bentlage, Tessa M. A. Peters, Arno van Rooij, Marleen C. D. G. Huigen, Siebolt de Boer, Ed van der Heeft, Leo A. J. Kluijtmans, Clara D. M. van Karnebeek, Ron A. Wevers, Giel Berden, Jos Oomens, Thomas J. Boltje, Karlien L. M. Coene, Jonathan Martens
Summary: The identification of disease biomarkers is crucial for diagnosing inborn errors of metabolism and understanding their pathophysiology. Research has found a class of Amadori rearrangement products that may serve as potential biomarkers for certain metabolic disorders.
COMMUNICATIONS BIOLOGY
(2021)
Correction
Genetics & Heredity
Saskia B. Wortmann, Szymon Zietkiewicz, Sergio Guerrero-Castillo, Rene G. Feichtinger, Matias Wagner, Jacqui Russell, Carolyn Ellaway, Dagmara Mroz, Hubert Wyszkowski, Denisa Weis, Iris Hannibal, Celina von Stulpnagel, Alfredo Cabrera-Orefice, Uta Lichter-Konecki, Jenna Gaesser, Randy Windreich, Kasiani C. Myers, Robert Lorsbach, Russell C. Dale, Soren Gersting, Carlos E. Prada, John Christodoulou, Nicole I. Wolf, Hanka Venselaar, Johannes A. Mayr, Ron A. Wevers
GENETICS IN MEDICINE
(2021)
Article
Genetics & Heredity
Saskia B. Wortmann, Szymon Zietkiewicz, Sergio Guerrero-Castillo, Rene G. Feichtinger, Matias Wagner, Jacqui Russell, Carolyn Ellaway, Dagmara Mroz, Hubert Wyszkowski, Denisa Weis, Iris Hannibal, Celina von Stuelpnagel, Alfredo Cabrera-Orefice, Uta Lichter-Konecki, Jenna Gaesser, Randy Windreich, Kasiani C. Myers, Robert Lorsbach, Russell C. Dale, Soren Gersting, Carlos E. Prada, John Christodoulou, Nicole I. Wolf, Hanka Venselaar, Johannes A. Mayr, Ron A. Wevers
Summary: This study investigated monoallelic CLPB variants in patients with a phenotype dominated by epilepsy, developmental issues, and 3-methylglutaconic aciduria. The results showed that these variants disrupt the refoldase and ATPase activity of CLPB, leading to a phenotypic spectrum centered around neurodevelopmental delay, seizures, and neutropenia, presumably mediated via HAX1.
GENETICS IN MEDICINE
(2021)
Article
Genetics & Heredity
Tessa Wassenberg, Ben P. H. Geurtz, Leo Monnens, Ron A. Wevers, Michel A. Willemsen, Marcel M. Verbeek
Summary: This study confirms that cerebrospinal fluid is the most informative body fluid to measure monoamine neurotransmitter metabolites when AADC or TH deficiency is suspected, and that routine follow-up of cerebrospinal fluid measurements to estimate treatment response is not needed. 3-O-methyldopa in dried blood spots and vanillactic acid in urine are promising peripheral biomarkers for diagnosis of AADC deficiency. However, in many patients with TH or AADC deficiency dopamine in urine is normal or increased thereby not reflecting the metabolic block. The value of serum prolactin for follow-up of AADC and TH deficiency should be further studied.
MOLECULAR GENETICS AND METABOLISM REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Nikolaos G. Bliziotis, Leo A. J. Kluijtmans, Gerjen H. Tinnevelt, Parminder Reel, Smarti Reel, Katharina Langton, Mercedes Robledo, Christina Pamporaki, Alessio Pecori, Josie Van Kralingen, Martina Tetti, Udo F. H. Engelke, Zoran Erlic, Jasper Engel, Timo Deutschbein, Svenja Noelting, Aleksander Prejbisz, Susan Richter, Jerzy Adamski, Andrzej Januszewicz, Filippo Ceccato, Carla Scaroni, Michael C. Dennedy, Tracy A. Williams, Livia Lenzini, Anne-Paule Gimenez-Roqueplo, Eleanor Davies, Martin Fassnacht, Hanna Remde, Graeme Eisenhofer, Felix Beuschlein, Matthias Kroiss, Emily Jefferson, Maria-Christina Zennaro, Ron A. Wevers, Jeroen J. Jansen, Jaap Deinum, Henri J. L. M. Timmers
Summary: This study aimed to establish signatures for different forms of endocrine hypertension (EHT) and investigate unbiased disease biomarkers. Plasma samples from 13 biobanks across seven countries were analyzed using untargeted NMR metabolomics. While signatures that could differentiate different forms of EHT were found, confounding effects related to sample center and age were also identified. Various approaches were applied to correct these confounding effects, but no biomarkers for differentiating primary hypertension from EHT could be identified.
Article
Biochemistry & Molecular Biology
Melanie T. Achleitner, Judith J. M. Jans, Laura Ebner, Johannes Spenger, Vassiliki Konstantopoulou, Rene G. Feichtinger, Karin Brugger, Doris Mayr, Ron A. Wevers, Christian Thiel, Saskia B. Wortmann, Johannes A. Mayr
Summary: Two siblings showed increased levels of galactose and related metabolites in neonatal screening, but diagnostic tests did not identify abnormalities in known disease-causing enzymes. Whole-exome sequencing revealed a homozygous missense variant in the PPA1 gene, which was found to reduce enzyme activity and protein stability. The observed metabolic derangement is hypothesized to be a mild manifestation of PPA1 deficiency.
Correction
Biochemistry & Molecular Biology
Shona Kalkman, Ron A. Wevers, Frits A. Wijburg, Mariska M. G. Leeflang
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Brechtje Hoegen, Alan Zammit, Albert Gerritsen, Udo F. H. Engelke, Steven Castelein, Maartje van de Vorst, Leo A. J. Kluijtmans, Marleen C. D. G. Huigen, Ron A. Wevers, Alain J. van Gool, Christian Gilissen, Karlien L. M. Coene, Purva Kulkarni
Summary: Inborn errors of metabolism are genetic diseases caused by defects in enzymes or cofactors, with untargeted metabolomics serving as a high throughput method for diagnostic screening. However, the complexity of metabolomics data poses a challenge for clinical applications.
Article
Clinical Neurology
Karlijn Bouman, Jeroen L. M. van Doorn, Jan T. Groothuis, Peter J. Wijkstra, Baziel G. M. van Engelen, Corrie E. Erasmus, Jonne Doorduin, Nicol C. Voermans
Summary: The majority of LAMA2-MD and all SELENON-RM patients had respiratory impairment. SELENON-RM patients showed lower respiratory function which was progressive, more prevalent mechanical ventilation, and more severe diaphragm atrophy and dysfunction than LAMA2-MD patients. Spirometry (FVC%, dVC) and respiratory muscle strength tests (SNIP) are useful in clinical care and as outcome measure in clinical trials.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2024)
Article
Clinical Neurology
Oliviero Bruni, Maria Breda, Emanuela Malorgio, Paolo Brambilla, Flavia Ceschin, Andrea Di Pilla, Maurizio Elia, Raffaele Ferri
Summary: This study aimed to describe the use of melatonin by Italian pediatricians in healthy children with chronic insomnia. The results showed that a high percentage of pediatricians prescribed melatonin, especially in children aged 1-2 years. The most common dosage was 1 mg/day and it was usually recommended to be taken 30 minutes before bedtime. Melatonin was often combined with sleep hygiene and was found to be effective in reducing difficulties falling asleep.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2024)
Article
Clinical Neurology
Lucie Sedlackova, Katalin Sterbova, Marketa Vlckova, Pavel Seeman, Jana Zarubova, Petr Marusic, Pavel Krsek, Hana Krijtova, Alena Musilova, Petra Lassuthova
Summary: In this study, whole exome sequencing (WES) was performed to identify causal variants for developmental and epileptic encephalopathies (DEEs) in patients whose genetic diagnosis was not determined by gene panel testing. The results showed that WES can successfully identify disease-causing variants, even after inconclusive gene panel testing. Detailed clinical evaluations and phenotype-genotype correlation studies were conducted to better understand the rare subtypes of DEEs.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2024)
