Article
Genetics & Heredity
Tarik Luisman, Tara Smith, Shawn Ritchie, Karen E. Malone
Summary: The study developed an RCDP incidence and prevalence model based on large-scale genetic diversity datasets, estimating the number of RCDP patients in the US and five largest European countries to be between 516 and 847, with PEX7 variants expected to contribute to the majority of cases. The model could help guide disease awareness and diagnosis efforts for this specific patient group.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Medical Laboratory Technology
Irene De Biase, Tatiana Yuzyuk, Wei Cui, Lauren M. Zuromski, Ann B. Moser, Nancy E. Braverman
Summary: Plasmalogens are glycerophospholipids with important roles in cellular processes, and their deficiency is associated with neurodegenerative diseases and peroxisome biogenesis disorders. A novel LC-MS/MS method was developed to quantify phosphoethanolamine plasmalogens in red blood cells, providing a specific and precise diagnostic tool. This method has the potential to enhance our understanding of disease pathogenesis and monitor therapy.
CLINICA CHIMICA ACTA
(2023)
Article
Genetics & Heredity
Adalgisa Cordisco, Elisabetta Pelo, Mariarosaria Di Tommaso, Roberto Biagiotti
Summary: Rhizomelic chondrodysplasia punctata (RCDP) is a rare disease with severe clinical manifestations and poor prognosis. This study identified new prenatal ultrasound findings and discovered a novel mutation in GNPAT, providing new evidence for the genetic mechanism of the disease.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Endocrinology & Metabolism
Wedad Fallatah, Monica Schouten, Christine Yergeau, Erminia Di Pietro, Marc Engelen, Hans R. Waterham, Bwee Tien Poll-The, Nancy Braverman
Summary: Rhizomelic chondrodysplasia punctata (RCDP) is a group of disorders caused by defects in genes encoding peroxisomal proteins required for plasmalogen biosynthesis. The severity of the disease correlates with erythrocyte plasmalogen levels, with almost undetectable levels in severe cases. Residual plasmalogen levels in milder forms are associated with better growth and development.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Medicine, General & Internal
Aiman M. Shawli, Abdulaziz T. Nazer, Yasir Khayyat, Mohammed G. Alqurashi, Fahad Hakami
Summary: Rhizomelic chondrodysplasia punctata (RCDP) is a rare peroxisomal autosomal recessive disorder characterized by skeletal abnormalities and intellectual disabilities. A 16-day-old girl with dysmorphic features was diagnosed with RCDP type 3 in Saudi Arabia. Early diagnosis and holistic management are essential for this distressing condition.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2021)
Article
Endocrinology & Metabolism
Peter J. Wegwerth, Amy L. White, Stephanie D. Stoway, Perry R. Loken, Devin Oglesbee, Dietrich Matern, Silvia Tortorelli, Kimiyo M. Raymond, Nancy E. Braverman, Dimitar K. Gavrilov
Summary: Measurement of plasmalogens is important in the biochemical diagnosis of RCDP and ZSD. A test method for simultaneous quantitation of plasmalogen species and their corresponding fatty acids has been developed. Normal reference ranges and preliminary disease ranges have been established. Integrated score and likelihood of disease can be generated using postanalytical interpretive tools to differentiate between RCDP and ZSD, along with review of clinical phenotype and other test results.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Genetics & Heredity
Muhammad Ali, Shahid Y. Khan, Tony A. Rodrigues, Tania Francisco, Xiaodong Jiao, Hang Qi, Firoz Kabir, Bushra Irum, Bushra Rauf, Asma A. Khan, Azra Mehmood, Muhammad Asif Naeem, Muhammad Zaman Assir, Muhammad Hassaan Ali, Mohsin Shahzad, Khaled K. Abu-Amero, Shehla Javed Akram, Javed Akram, Sheikh Riazuddin, Saima Riazuddin, Michael L. Robinson, Myriam Baes, Jorge E. Azevedo, J. Fielding Hejtmancik, S. Amer Riazuddin
Summary: A novel missense mutation in PEX5 was identified in a large family, resulting in defective import of PTS2 cargo proteins into peroxisomes, leading to congenital cataracts and developmental defects.
Review
Genetics & Heredity
Ezgi Gokpinar Ili, Alper Gezdirici, Erminia Di Pietro, Christine Yergeau, Nancy Braverman
Summary: Rhizomelic chondrodysplasia punctata (RCDP) is a group of peroxisomal disorders caused by plasmalogen synthesis defects. Patients with RCDP present with various clinical features including short stature, epiphyseal calcifications, cataracts, and intellectual disability. This study reports two new patients with RCDP3 and their novel AGPS gene variants.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Review
Multidisciplinary Sciences
Joseph A. Barnes-Velez, Fatma Betul Aksoy Yasar, Jian Hu
Summary: This article summarizes the role of lipid metabolism and molecular determinants of myelin lipid homeostasis in myelination and maintenance. It also highlights the implications of myelin lipid dysmetabolism in human diseases, including hereditary leukodystrophies, neuropathies, and Alzheimer's disease.
Article
Medicine, Research & Experimental
Quentin Raas, Malu-Clair van de Beek, Sonja Forss-Petter, Inge M. E. Dijkstra, Abigail Deschiffart, Briana C. Freshner, Tamara J. Stevenson, Yorrick R. J. Jaspers, Liselotte Nagtzaam, Ronald J. A. Wanders, Michel van Weeghel, Joo-Yeon Engelen-Lee, Marc Engelen, Florian Eichler, Johannes Berger, Joshua L. Bonkowsky, Stephan Kemp
Summary: The study found that rerouting saturated fatty acids to monounsaturated fatty acids can alleviate lipid toxicity in X-linked adrenoleukodystrophy (ALD). The drug chloroquine increased the expression of the enzyme regulating saturated fatty acid saturation status, relieving toxicity. Additionally, activating liver X receptor (LXR) can also convert saturated fatty acids to monounsaturated fatty acids.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Multidisciplinary Sciences
Isabelle Weinhofer, Paulus Rommer, Bettina Zierfuss, Patrick Altmann, Martha Foiani, Amanda Heslegrave, Henrik Zetterberg, Andreas Gleiss, Patricia L. Musolino, Yi Gong, Sonja Forss-Petter, Thomas Berger, Florian Eichler, Patrick Aubourg, Wolfgang Koehler, Johannes Berger
Summary: X-ALD is a highly variable, progressive neurodegenerative disorder. In this study, neurofilament light chain protein (NfL) was identified as a potential early distinguishing biomarker.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Laura Rodriguez-Pascau, Anna Vilalta, Marc Cerrada, Estefania Traver, Sonja Forss-Petter, Isabelle Weinhofer, Jan Bauer, Stephan Kemp, Guillem Pina, Silvia Pascual, Uwe Meya, Patricia L. Musolino, Johannes Berger, Marc Martinell, Pilar Pizcueta
Summary: Leriglitazone shows promising neuroprotective effects in X-ALD, reducing oxidative stress and toxicity in primary neurons and astrocytes. It also improves motor function, restores markers of oxidative stress and inflammation in spinal cord tissues, and decreases neurological disability in animal models of neuroinflammation.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Neurosciences
Fabian Dorninger, Frederic M. Vaz, Hans R. Waterham, Jan B. van Klinken, Gerhard Zeitler, Sonja Forss-Petter, Johannes Berger, Christoph Wiesinger
Summary: Phospholipid transport from the periphery to the brain is a relatively understudied topic. Oral administration of alkylglycerols may replenish ether lipids in peripheral tissues, but does not effectively address plasmalogen deficiency in the brain. Modulation of efflux transport across the blood-brain barrier may have potential therapeutic implications for disorders related to ether lipid deficiency.
BRAIN RESEARCH BULLETIN
(2022)
Article
Cell Biology
Bernhard Hochreiter, Hugo Malagon-Vina, Johannes A. Schmid, Johannes Berger, Markus Kunze
Summary: The competition assay based on FRET provides a powerful tool for studying protein recognition and interactions in living cells. This method allows quantifying investigations of binding affinities and can overcome limitations of previous FRET approaches. The study reveals the binding strengths between PEX5 and various cargo proteins, as well as the impact of N-terminal domains on the interaction strength.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Fabian Dorninger, Ernst R. Werner, Johannes Berger, Katrin Watschinger
Summary: Due to their unique chemical structure, plasmalogens exhibit distinct biological features and require specialized pathways for biosynthesis and metabolism. Despite some progress, many questions about the regulation of plasmalogen metabolism and their distribution in mammals remain unanswered. This article summarizes current evidence on the regulation of enzymes involved in plasmalogen biosynthesis and degradation, as well as the turnover of plasmalogens, with a focus on plasmalogen traffic in mammals.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biology
Isabelle Weinhofer, Agnieszka Buda, Markus Kunze, Zsofia Palfi, Matthaus Traunfellner, Sarah Hesse, Andrea Villoria-Gonzalez, Jorg Hofmann, Simon Hametner, Gunther Regelsberger, Ann B. Moser, Florian Eichler, Stephan Kemp, Jan Bauer, Joern-Sven Kuehl, Sonja Forss-Petter, Johannes Berger
Summary: The study highlights the importance of ABCD1 in viral infection and host defense, using Epstein-Barr virus (EBV) infection of human B cells, which could be applicable to other herpes- and coronaviruses.
COMMUNICATIONS BIOLOGY
(2022)
Article
Neurosciences
Ernst R. Werner, Danielle Swinkels, Viktorija Juric, Fabian Dorninger, Myriam Baes, Markus A. Keller, Johannes Berger, Katrin Watschinger
Summary: Based on the findings from mouse experiments, the dysfunction of peroxisomes in the liver does not affect the levels of plasmalogens in plasma and tissues. Instead, there is an increase in plasmenylcholine species in the liver. Therefore, this study does not support the hypothesis that hepatocytes supply plasmalogens to tissues.
BRAIN RESEARCH BULLETIN
(2023)
Article
Immunology
Lingjia Kong, Vladislav Pokatayev, Ariel Lefkovith, Grace T. Carter, Elizabeth A. Creasey, Chirag Krishna, Sathish Subramanian, Bharati Kochar, Orr Ashenberg, Helena Lau, Ashwin N. Ananthakrishnan, Daniel B. Graham, Jacques Deguine, Ramnik J. Xavier
Summary: Crohn's disease is a chronic gastrointestinal disease with increasing prevalence worldwide. By analyzing over 700,000 cells from the intestines of 71 donors, researchers identified cell-type-specific transcriptional heterogeneity and organ-specific responses to inflammation. Immune changes occurred mostly in cell composition, while transcriptional changes dominated in epithelial and stromal cells. The study also identified markers of fibrotic complications and potential regulators for therapeutic development.
Article
Biochemistry & Molecular Biology
Fabian Dorninger, Attila Kiss, Peter Rothauer, Alexander Stiglbauer-Tscholakoff, Stefan Kummer, Wedad Fallatah, Mireia Perera-Gonzalez, Ouafa Hamza, Theresa Koenig, Michael B. Bober, Tiscar Cavalle-Garrido, Nancy E. Braverman, Sonja Forss-Petter, Christian Pifl, Jan Bauer, Reginald E. Bittner, Thomas H. Helbich, Bruno K. Podesser, Hannes Todt, Johannes Berger
Summary: The deficiency in ether lipids can cause severe symptoms in humans and the mouse model has been used to study the pathophysiology of the disease. However, the exact role of ether lipids in the cardiac tissue is still unknown. This study found that ether lipid deficiency can lead to cardiac abnormalities in both mice and human patients, but the manifestations are heterogeneous and differ between the two.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Bettina Zierfuss, Agnieszka Buda, Andrea Villoria-Gonzalez, Maxime Logist, Jure Fabjan, Patricia Parzer, Claire Battin, Streggi Vandersteene, Inge M. E. Dijkstra, Petra Waidhofer-Soellner, Katharina Grabmeier-Pfistershammer, Peter Steinberger, Stephan Kemp, Sonja Forss-Petter, Johannes Berger, Isabelle Weinhofer
Summary: VLCFA accumulation in X-ALD is associated with macrophage activation through CD36-mediated uptake, leading to pro-inflammatory responses.
JOURNAL OF NEUROINFLAMMATION
(2022)
Editorial Material
Cell Biology
Fabian Dorninger, Johannes Berger, Masanori Honsho
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Neurosciences
Ksenija Martinovic, Jan Bauer, Markus Kunze, Johannes Berger, Sonja Forss-Petter
Summary: X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disease caused by mutations in the ABCD1 gene. We combined two mouse models to investigate the role of X-ALD oligodendrocytes in demyelination. We found that Abcd1 deficient mice exhibited increased vulnerability in the early demyelinating phase, leading to more severe axonal damage.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)