Article
Medicine, General & Internal
Federica Boraldi, Vittoria Murro, Francesco Demetrio Lofaro, Dario Pasquale Mucciolo, Sonia Costa, Laura Pavese, Daniela Quaglino
Summary: ABCC6 rare sequence variants were found throughout the entire gene in a cohort of Italian PXE patients. The severity of clinical phenotype in PXE patients was found to be age-dependent, with in-depth ophthalmological examinations providing insight into disease progression and allowing for better patient stratification.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Cell Biology
David Czimer, Klaudia Porok, Daniel Csete, Zsolt Gyure, Viktoria Lavro, Krisztina Fulop, Zelin Chen, Hella Gyergyak, Gabor E. Tusnady, Shawn M. Burgess, Attila Mocsai, Andras Varadi, Mate Varga
Summary: Calcification is a significant health issue associated with aging, cancer, and autoimmune diseases, with both environmental and genetic factors at play. Understanding the phenomenon is essential for developing effective therapeutic approaches. Pseudoxanthoma elasticum (PXE) is a rare genetic disease without a cure, but research shows that zebrafish could serve as a new model for studying the disease.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Medicine, General & Internal
Eszter Kozak, Jonas W. Bartstra, Pim A. de Jong, Willem P. T. M. Mali, Krisztina Fulop, Natalia Tokesi, Viola Pomozi, Sara Risseeuw, Jeannette Ossewaarde-van Norel, Redmer van Leeuwen, Andras Varadi, Wilko Spiering
Summary: ABCC6 gene mutations in patients with pseudoxanthoma elasticum (PXE) were found to be associated with lower plasma inorganic pyrophosphate (PPi) levels. However, no association between PPi levels and PXE phenotypes or ABCC6 genotypes was found in this study.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Max Jonathan Stumpf, Nadjib Schahab, Georg Nickenig, Dirk Skowasch, Christian Alexander Schaefer
Summary: PXE is a rare genetic metabolic disease characterized by skin lesions, choroidal neovascularization, and early-onset arterial calcification. It is caused by recessively transmitted pathogenic variants of the ABCC6 gene, leading to a deficiency of ABCC6 protein. Treatments for PXE are either outdated or not widely available, presenting challenges for clinical physicians and patients.
Article
Ophthalmology
Anne-Sophie Loewinger, Maximilian Pfau, Philipp Herrmann, Frank G. Holz, Kristina Pfau
Summary: This study aims to quantify choriocapillaris flow alterations in patients with pseudoxanthoma elasticum (PXE) in pre-atrophic stages and its association with structural changes of the choroid and outer retina. The results showed significantly higher choriocapillaris flow signal deficits (FDs) in PXE patients compared to controls, with increasing age and retinal location. Choroidal thickness (CT) was not significantly different between the two groups, and larger FDs values were associated with significant thinning of the overlying photoreceptor layers.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Article
Medicine, General & Internal
Lukas Nollet, Matthias Van Gils, Suzanne Fischer, Laurence Campens, Swapna Karthik, Andreas Pasch, Julie De Zaeytijd, Bart P. Leroy, Daniel Devos, Tine De Backer, Paul J. Coucke, Olivier M. Vanakker
Summary: This study evaluated the potential of serum calcification propensity T50 as a biomarker for disease severity in patients with pseudoxanthoma elasticum (PXE). The results showed that shorter serum T50 was associated with a more severe phenotype in PXE patients. This suggests that serum T50 might be a clinically relevant biomarker in PXE, which could be of importance for future therapeutic trials.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Medicine, General & Internal
Georges Leftheriotis, Nastassia Navasiolava, Laetitia Clotaire, Christophe Duranton, Olivier Le Saux, Said Bendahhou, Audrey Laurain, Isabelle Rubera, Ludovic Martin
Summary: PXE is a rare metabolic disorder characterized by progressive calcification in the skin, the Bruch's membrane, and the vasculature. This study found a deficit in plasma PPi levels in PXE patients, with a correlation to age and gender. However, arterial calcification showed a weak connection to PPi levels, with age being the main determinant of disease severity.
JOURNAL OF CLINICAL MEDICINE
(2022)
Editorial Material
Dermatology
Aiping Zheng, Patrick H. Thibodeau
Summary: Significant progress has been made in understanding pseudoxanthoma elasticum (PXE), and researchers have proposed a novel in vivo model for characterizing and annotating ABCC6 variants.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Editorial Material
Dermatology
Gabrielle Brokamp, Mari Mori, Esteban Fernandez Faith
Summary: This case report describes hypopigmented yellow, soft, and smooth papules coalescing into plaques on the lateral neck.
Article
Dermatology
Ida Joely Jacobs, Diana Li, Mattias E. Ivarsson, Jouni Uitto, Qiaoli Li
Summary: The study demonstrated that INS-3001 effectively prevents and stabilizes ectopic calcification in a mouse model of Pseudoxanthoma elasticum (PXE). Different doses of INS-3001 showed dose-dependent inhibition of calcification, with both subcutaneous injections and osmotic pump implantation proving effective in treatment.
EXPERIMENTAL DERMATOLOGY
(2021)
Review
Dermatology
Hongbin Luo, Masoomeh Faghankhani, Yi Cao, Jouni Uitto, Qiaoli Li
Summary: In the past two decades, significant progress has been made in understanding the molecular basis and pathomechanistic details of pseudoxanthoma elasticum (PXE). Genetic modifiers have been identified to explain the phenotypic heterogeneity of PXE, in addition to pathogenic variants in the ABCC6 gene. The genetic complexity of PXE is further complicated by PXE-like phenotypes caused by variants in other ectopic mineralization-associated genes.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Dermatology
Ida Joely Jacobs, Zhiliang Cheng, Douglas Ralph, Kevin O'Brien, Lisa Flaman, Jennifer Howe, David Thompson, Jouni Uitto, Qiaoli Li, Yves Sabbagh
Summary: This study found that restoring plasma PPi levels can prevent ectopic calcification in a mouse model of Pseudoxanthoma elasticum (PXE). INZ-701 increases plasma ENPP1 activity and PPi levels, leading to significantly reduced calcification in the muzzle skin of the mice.
EXPERIMENTAL DERMATOLOGY
(2022)
Article
Medicine, General & Internal
Matthias Van Gils, Justin Depauw, Paul J. J. Coucke, Shari Aerts, Shana Verschuere, Lukas Nollet, Olivier M. M. Vanakker
Summary: Pseudoxanthoma elasticum (PXE) is a rare calcification disorder caused by ABCC6 mutations. Reduced levels of PPi were found in PXE patients and carriers, but it is not a predictive biomarker for disease severity and progression.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Genetics & Heredity
Saku Pelttari, Suvi Vaaramaki, Olivier Vanakker, Shana Verschuere, Hannu Uusitalo, Heini Huhtala, Tero Hinkka, Ilkka Porsti, Pasi Nevalainen
Summary: The study evaluated the prevalence of PXE in Finland and found a lower prevalence rate compared to other countries. Patients with high conventional cardiovascular risk had more visual and vascular complications. Various ABCC6 gene variants were identified, and vascular malformations may be an unrecognized feature of PXE.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Cardiac & Cardiovascular Systems
Jonas W. Bartstra, Sara Risseeuw, Pim A. de Jong, Bram van Os, Lianne Kalsbeek, Chris Mol, Annette F. Baas, Shana Verschuere, Olivier Vanakker, Ralph J. Florijn, Jeroen Hendrikse, Willem Mali, Saskia Imhof, Jeannette Ossewaarde-van Norel, Redmer van Leeuwen, Wilko Spiering
Summary: The study revealed that PXE patients with a mixed genotype showed less severe arterial and ophthalmological phenotypes compared to patients with two truncating variants in the ABCC6 gene. Further research into environmental and genetic modifiers may help explain the unexplained phenotypic variability.
Review
Biochemistry & Molecular Biology
Celine Koster, Kimberley E. Wever, Ellie L. Wagstaff, Koen T. van den Hurk, Carlijn R. Hooijmans, Arthur A. Bergen
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Ophthalmology
Xuan-Thanh-An Nguyen, Mays Talib, Caroline van Cauwenbergh, Mary J. van Schooneveld, Marta Fiocco, Jan Wijnholds, Jacoline B. Ten Brink, Ralph J. Florijn, Nicoline E. Schalij-Delfos, Gislin Dagnelie, Maria M. van Genderen, Elfride de Baere, Magda A. Meester-Smoor, Julie De Zaeytijd, Irina Balikova, Alberta A. Thiadens, Carel B. Hoyng, Caroline C. Klaver, L. Ingeborgh van den Born, Arthur A. Bergen, Bart P. Leroy, Camiel J. F. Boon
Summary: By reviewing medical charts of 100 patients with autosomal dominant RHO-associated RP, the study found significant differences in disease progression between patients with generalized RP phenotype and those with sector RP phenotype in terms of central visual field, suggesting that the optimal window for intervention should be before the 5th decade of life. The study also suggests that the PR + RPE complex could be a potential surrogate endpoint for BCVA in future studies.
RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
(2021)
Article
Genetics & Heredity
Suzanne E. de Bruijn, Jeroen J. Smits, Chang Liu, Cornelis P. Lanting, Andy J. Beynon, Joelle Blankevoort, Jaap Oostrik, Wouter Koole, Erik de Vrieze, Cor W. R. J. Cremers, Frans P. M. Cremers, Susanne Roosing, Helger G. Yntema, Henricus P. M. Kunst, Bo Zhao, Ronald J. E. Pennings, Hannie Kremer
Summary: Adult-onset progressive hearing loss is highly heritable and has been identified in 12 families in the Netherlands as an autosomal dominant trait. A 12-nucleotide in-frame deletion in the RIPOR2 gene was found to be a significant cause of this type of hearing loss, affecting protein localization in cochlear hair cells and morphology.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Multidisciplinary Sciences
Philip E. Wagstaff, Anneloor L. M. A. ten Asbroek, Jacoline B. ten Brink, Nomdo M. Jansonius, Arthur A. B. Bergen
Summary: Genetically complex ocular neuropathies like glaucoma are a major global cause of visual impairment with no effective treatment available. Retinal organoids are increasingly used for experimental therapies, but current methods may take a long time to develop and mature.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Bettina Ibold, Janina Tiemann, Isabel Faust, Uta Ceglarek, Julia Dittrich, Theo G. M. F. Gorgels, Arthur A. B. Bergen, Olivier Vanakker, Matthias Van Gils, Cornelius Knabbe, Doris Hendig
Summary: The genetic link between ABCC6 mutations and PXE has been established, with studies showing altered cholesterol levels and an increased risk of coronary artery diseases. ABCC6 deficiency in mice leads to reduced serum cholesterol and phytosterol levels, activated cholesterol biosynthesis, and decreased HDL cholesterol levels. This suggests that ABCC6 plays a crucial role in cholesterol homeostasis and impaired cholesterol metabolism may be a key mechanism in PXE manifestation.
SCIENTIFIC REPORTS
(2021)
Article
Ophthalmology
Mays Talib, Mary J. van Schooneveld, Jan Wijnholds, Maria M. van Genderen, Nicoline E. Schalij-Delfos, Herman E. Talsma, Ralph J. Florijn, Jacoline B. ten Brink, Frans P. M. Cremers, Alberta A. H. J. Thiadens, L. Ingeborgh van den Born, Carel B. Hoyng, Magda A. Meester-Smoor, Arthur A. Bergen, Camiel J. F. Boon
Summary: This study investigated the retinal structure and function in patients with CRB1-associated retinal dystrophies (RD) and explored potential clinical endpoints. Despite a generally severe course, symptom onset and central visual function varied, even at advanced ages. Phenotypes may differ within the same family, and longitudinal imaging and functional studies are needed to determine appropriate endpoints for a clinical trial.
ACTA OPHTHALMOLOGICA
(2021)
Article
Genetics & Heredity
Ilaria Parenti, Daphne Lehalle, Caroline Nava, Erin Torti, Elsa Leitao, Richard Person, Takeshi Mizuguchi, Naomichi Matsumoto, Mitsuhiro Kato, Kazuyuki Nakamura, Stella A. de Man, Heidi Cope, Vandana Shashi, Undiagnosed Diseases Network, Jennifer Friedman, Pascal Joset, Katharina Steindl, Anita Rauch, Irena Muffels, Peter M. van Hasselt, Florence Petit, Thomas Smol, Gwenael Le Guyader, Frederic Bilan, Arthur Sorlin, Antonio Vitobello, Christophe Philippe, Ingrid M. B. H. van de Laar, Marjon A. van Slegtenhorst, Philippe M. Campeau, Ping Yee Billie Au, Mitsuko Nakashima, Hirotomo Saitsu, Tatsuya Yamamoto, Yumiko Nomura, Raymond J. Louie, Michael J. Lyons, Amy Dobson, Astrid S. Plomp, M. Mahdi Motazacker, Frank J. Kaiser, Andrew T. Timberlake, Sabine A. Fuchs, Christel Depienne, Cyril Mignot
Summary: The CHD5 gene, located in the critical 1p36 microdeletion region, encodes a subunit of the NuRD complex required for neuronal development. Variants in this gene were identified in 16 unrelated individuals, showing features like intellectual disability, speech delay, and epilepsy.
Article
Biochemistry & Molecular Biology
Nemanja Milicevic, Ouafa Ait-Hmyed Hakkari, Udita Bagchi, Cristina Sandu, Aldo Jongejan, Perry D. Moerland, Jacoline B. ten Brink, David Hicks, Arthur A. Bergen, Marie-Paule Felder-Schmittbuhl
Summary: The study showed that Per1 and Per2 are essential clock components for driving photoreceptor outer segment phagocytosis, and this process may be transcriptionally driven by the retinal pigment epithelium (RPE). No differentially expressed genes were found in photoreceptors, while several genes were differentially expressed in the RPE, both in wild type and Per1, Per2 double mutant mice. STRING analysis identified a group of interacting genes potentially involved in driving photoreceptor outer segment phagocytosis in the RPE.
Review
Biochemistry & Molecular Biology
Philip E. Wagstaff, Andrea Heredero Berzal, Camiel J. E. Boon, Peter M. J. Quinn, Anneloor L. M. A. ten Asbroek, Arthur A. Bergen
Summary: Researchers manipulate key signaling pathways of early retinal development using retinal organoids, but the use of different additives has led to low reproducibility and high variability in experimental results.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Janine Reurink, Adrian Dockery, Dominika Ozieblo, G. Jane Farrar, Monika Oldak, Jacoline B. ten Brink, Arthur A. Bergen, Tuula Rinne, Helger G. Yntema, Ronald J. E. Pennings, L. Ingeborgh van den Born, Marco Aben, Jaap Oostrik, Hanka Venselaar, Astrid S. Plomp, M. Imran Khan, Erwin van Wijk, Frans P. M. Cremers, Susanne Roosing, Hannie Kremer
Summary: This study assessed unscreened or incompletely screened USH2 and arRP cases for likely pathogenic USH2A variants using MIP-based sequencing, successfully identifying (likely) pathogenic variants in a majority of cases. The effectiveness of MIP-based sequencing as a screening tool for USH2A was confirmed, with seven unexplained cases selected for future analysis with whole genome sequencing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Celine Koster, Koen T. van den Hurk, Colby F. Lewallen, Mays Talib, Jacoline B. ten Brink, Camiel J. F. Boon, Arthur A. Bergen
Summary: A pigmented knockout rat model for LRAT gene was developed using CRISPR/Cas9, showing progressively reduced retinal structure and function in LRAT knockout animals.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Ophthalmology
Shumet T. Gegnaw, Cristina Sandu, Jorge Mendoza, Arthur A. Bergen, Marie-Paule Felder-Schmittbuhl
Summary: The retinal circadian system, consisting of clocks in different retinal cell types, regulates rhythmic processes in the retina. Studies on mice with rod-specific knockout of Bmal1 show that the circadian clock in rods plays a crucial role in regulating visual processing in a cell autonomous manner. This study suggests that the clock in rods influences visual function by modulating retinal responses to light stimuli.
EXPERIMENTAL EYE RESEARCH
(2021)
Article
Developmental Biology
Amandine Bery, Udita Bagchi, Arthur A. Bergen, Marie-Paule Felder-Schmittbuhl
Summary: This article explores the influence of circadian clocks on the development and diseases of the retina. The study reveals that clock genes play a role in different stages of retinal development and can modulate pathological processes.
DEVELOPMENTAL BIOLOGY
(2022)
Article
Biology
Nemanja Milicevic, Arthur A. Bergen, Marie-Paule Felder-Schmittbuhl
Summary: Light can synchronize an animal's sleep-wake cycle and directly influence its activity level. High illumination levels decrease activity in mice, and the Per1 gene plays a crucial role in suppressing negative masking responses.
CHRONOBIOLOGY INTERNATIONAL
(2022)
Article
Endocrinology & Metabolism
Carline E. Tacke, Suzanne W. J. Terheggen-Lagro, Annemieke M. Boot, Astrid S. Plomp, Abeltje M. Polstra, Rick R. van Rijn, Peter A. A. Struijs, Henk van den Berg, Christiaan F. Mooij
Summary: The patient has a chromosome duplication involving the PTHLH gene, resulting in multiple skeletal abnormalities, including chondrodysplasia and severe chest deformity. The chest deformity causes severe pulmonary symptoms, and imaging studies during follow-up revealed increasing number of skeletal lesions.
