Article
Genetics & Heredity
Hans R. Waterham, Janet Koster, Merel S. Ebberink, Pavel Jesina, Jiri Zeman, Lenka Noskova, Stanislav Kmoch, Perrine Devic, David Cheillan, Ronald J. A. Wanders, Sacha Ferdinandusse
Summary: We report two unrelated patients with autosomal dominant Zellweger spectrum disorders (ZSDs). Biochemical and genetic studies revealed single heterozygous de novo variants in the PEX14 genes of both patients, leading to mRNA mis-splicing and expression of truncated PEX14 proteins. Functional studies demonstrated the dominant-negative effect of these truncated proteins on peroxisome functioning, which was restored by inhibition of pexophagy.
GENETICS IN MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Delara Akhter, Yuchan Zhang, Jianping Hu, Ronghui Pan
Summary: Protein ubiquitination plays a crucial role in regulating diverse cellular processes in eukaryotic organisms, including growth, development, and stress response. Despite its importance, the mechanisms underlying protein ubiquitination in peroxisomes, especially in plants, are poorly understood. This review provides a comprehensive summary of the current knowledge on the involvement of protein ubiquitination in peroxisome biology, focusing on plants.
JOURNAL OF INTEGRATIVE PLANT BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mirco Schilff, Yelena Sargsyan, Julia Hofhuis, Sven Thoms
Summary: The study explores the impact of stop codon context on the treatment strategy for genetic premature termination codon diseases and finds that SCC plays a significant role in readthrough stimulation and drug concentration selection.
Article
Cell Biology
Stephanie A. A. Mauriac, Thibault Peineau, Aamir Zuberi, Cathleen Lutz, Gwenaelle S. G. Geleoc
Summary: Peroxisome Biogenesis Disorders (PBD) and Zellweger syndrome spectrum disorders (ZSD) are rare genetic disorders that affect sensory hair cells and hearing. Mutations in the PEX1 gene lead to oxidative stress, which impairs hair cells in the inner ear and causes hearing loss. Conditional knockout mice studies demonstrate the critical role of Pex1 in the development and auditory function of inner hair cells.
Article
Genetics & Heredity
Paola Borgia, Simona Baldassari, Nicoletta Pedemonte, Ebba Alkhunaizi, Gianluca D'Onofrio, Domenico Tortora, Elisa Cali, Paolo Scudieri, Ganna Balagura, Ilaria Musante, Maria Cristina Diana, Marina Pedemonte, Maria Stella Vari, Michele Iacomino, Antonella Riva, Roberto Chimenz, Giuseppe D. Mangano, Mohammad Hasan Mohammadi, Mehran Beiraghi Toosi, Farah Ashrafzadeh, Shima Imannezhad, Ehsan Ghayoor Karimiani, Andrea Accogli, Maria Cristina Schiaffino, Mohamad Maghnie, Miguel Angel Soler, Karl Echiverri, Charles K. Abrams, Pasquale Striano, Sara Fortuna, Reza Maroofian, Henry Houlden, Federico Zara, Chiara Fiorillo, Vincenzo Salpietro
Summary: This study reports the clinical and genetic spectrum of PEX13-related ZSDs and highlights the contribution of various disease mechanisms, including secondary mitochondrial dysfunction, to PEX13-related clinical phenotypes.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Cell Biology
Femke C. C. Klouwer, Kim D. Falkenberg, Rob Ofman, Janet Koster, Demi van Gent, Sacha Ferdinandusse, Ronald J. A. Wanders, Hans R. Waterham
Summary: This study investigated the potential use of autophagy inhibitors as a treatment option for PBD-ZSD patients carrying the PEX1-G843D mutation. However, the results showed that autophagy inhibitors did not improve peroxisomal functions, and in fact worsened metabolic functions and protein import in cells with the mutation. The study suggests that L-arginine remains a promising therapeutic compound for PBD-ZSD patients.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Anesthesiology
Feng Pan, Ming Liu, Edward W. Randell, Proton Rahman, Graeme Jones, Guangju Zhai
Summary: Metabolic dysfunction has been suggested to be involved in musculoskeletal pain, with sphingomyelin metabolism found to play a role in the pathogenesis of multisite musculoskeletal pain (MSMP). Furthermore, the circulating level of SM C18:1 could serve as a potential marker in the management of MSMP.
Article
Cell Biology
Tanguy Demaret, Jonathan Evraerts, Joachim Ravau, Martin Roumain, Giulio G. Muccioli, Mustapha Najimi, Etienne M. Sokal
Summary: The study evaluated the short-term effects of hepatocyte transplantation in a mouse model mimicking mild Zellweger spectrum disorder (ZSD). Although the results showed promising outcomes, there were no significant modifications in clinical and biochemical parameters. Future optimizations are needed to improve hepatocyte engraftment in the ZSD mouse liver. The mouse model demonstrated robustness for evaluating liver-targeted therapies for ZSD.
Article
Neurosciences
Gianna Fote, Jie Wu, Mark Mapstone, Fabio Macciardi, Massimo S. Fiandaca, Howard J. Federoff
Summary: The study evaluated plasma SM species in LOAD patients, finding a significant reduction of the metabolite SM OHC14:1 in preclinical AD patients. This suggests that plasma sphingomyelin levels may play a significant role in early diagnosis of AD.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Sport Sciences
Rongsong Li, Alessandra Adami, Chih-Chiang Chang, Chi-Hong Tseng, Tzung K. Hsiai, Harry B. Rossiter
Summary: The study found significant decreases in muscle oxidative capacity and physical activity levels in patients with severe COPD compared to smokers with normal lung function. The research also revealed a close association between metabolic abnormalities and impaired mitochondrial function and the accumulation of triacylglycerides in severe COPD patients.
MEDICINE & SCIENCE IN SPORTS & EXERCISE
(2021)
Article
Cell Biology
Kuo-Hsuan Chang, Mei-Ling Cheng, Hsiang-Yu Tang, Cheng-Yu Huang, Hsiu-Chuan Wu, Chiung-Mei Chen
Summary: Using targeted metabolomics analysis, this study identified new blood biomarker candidates for Parkinson's disease (PD) and found significant correlations between these biomarkers and disease progression and clinical manifestations of PD.
Review
Pediatrics
Ana-Maria Slanina, Adorata-Elena Coman, Dana-Teodora Anton-Paduraru, Elena Popa, Carmen-Liliana Barbacariu, Otilia Novac, Antoneta Dacia Petroaie, Agnes-Iacinta Bacusca, Mihaela Manole, Adriana Cosmescu
Summary: The aim of this paper is to describe the temporal progression and clinical picture of a 2-year-old child with infantile Refsum disease, as well as the diagnostic procedures performed. The child presented multiple hematologic, metabolic, and developmental complications and progressive disabilities. Genetic testing revealed a mutation of the PEX6 gene, and the metabolic profile was consistent with the diagnosis. Particularly, the child also presented altered coagulation factors and developed a spontaneous brain hemorrhage. The clinical picture includes several neurological, ophthalmological, digestive, cutaneous, and endocrine disorders.
Review
Genetics & Heredity
Janaina Nogueira Anderson, Zineb Ammous, Yasemen Eroglu, Erick Hernandez, James Heubi, Ryan Himes, Sirish Palle
Summary: Zellweger spectrum disorders (ZSDs) are rare, autosomal recessively inherited disorders characterized by peroxisomal dysfunction. Liver disease is a major contributor to morbidity and mortality in patients with ZSDs, and Cholbam has been shown to be a safe and effective treatment for improving liver function in these patients. It is recommended to initiate Cholbam therapy early in patients without advanced liver disease to prevent systemic impacts of hepatic damage.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Genetics & Heredity
Anuhya Anne, Sonal Saxena, Kommu Naga Mohan
Summary: Large DNA methylation changes were found in the gene promoters of cerebellum tissues of patients with autism spectrum disorder (ASD), including genes involved in peroxisome function. This supports the hypothesis that impaired peroxisome function/biogenesis is associated with ASD. Similar approaches could be used to identify rare epimutations in ASD and other complex disorders.
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
Biochemical Research Methods
Lillian R. Thistlethwaite, Varduhi Petrosyan, Xiqi Li, Marcus J. Miller, Sarah H. Elsea, Aleksandar Milosavljevic
Summary: The paper introduces a novel information-theoretic formulation of identifying highly connected subsets within a weighted graph without the need for computationally costly permutation testing. The proposed algorithm, CTD Connect the Dots, uses data compression to detect highly connected subsets within a given set of nodes.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Genetics & Heredity
John Odom, Hitha Amin, Charul Gijavanekar, Sarah H. Elsea, Stephen Kralik, Javier Chinen, Yuezhen Lin, Amber Meshell Mayfield Yates, Elizabeth Mizerik, Lorraine Potocki, Fernando Scaglia
Summary: Sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD) is caused by pathogenic variants in the TRNT1 gene, leading to mitochondrial and cytosolic tRNA processing disorders. In addition to the main symptoms, patients may also exhibit growth hormone deficiency-related hypoglycemia, indicating the complexity and variability of the disease. Metabolomics analysis may provide insights into potential biochemical markers for SIFD.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Cell Biology
Michael S. Dahabieh, Fan Huang, Christophe Goncalves, Raul Ernesto Flores Gonzalez, Sathyen Prabhu, Alicia Bolt, Erminia Di Pietro, Elie Khoury, John Heath, Zi Yi Xu, Joelle Remy-Sarrazin, Koren K. Mann, Alexandre Orthwein, Francois-Michel Boisvert, Nancy Braverman, Wilson H. Miller, Sonia V. del Rincon
Summary: Promoting autophagy-mediated degradation of specific proteins and organelles can induce apoptosis in cancer cells or sensitize them to therapy. Targeting peroxisome homeostasis through increased pexophagy can enhance sensitivity to treatment, as shown in lymphoma, lung cancer, and melanoma models.
Article
Audiology & Speech-Language Pathology
John Lee, Christine Yergeau, Kosuke Kawai, Nancy Braverman, Gwenaelle S. G. Geleoc
Summary: This retrospective natural history study aimed to characterize the hearing loss associated with PBD-ZSD. The majority of PBD-ZSD patients in this study presented with moderately-severe to severe hearing loss and relatively slow rates of longitudinal changes in hearing sensitivity. Improvements in hearing thresholds were observed with use of hearing aid amplification. The study highlights the need for more comprehensive assessments of hearing loss in PBD-ZSD patients.
Article
Genetics & Heredity
Tania Cruz Marino, Jessica Tardif, Josianne Leblanc, Janie Lavoie, Pascal Morin, Michel Harvey, Marie-Jacqueline Thomas, Annabelle Pratte, Nancy Braverman
Summary: The French-Canadian population in Saguenay-Lac-Saint-Jean is known for its homogenous genetic background, and the hereditary causes of hearing loss have not been explored in this population before. Through a regional clinical evaluation strategy and a comprehensive multigene panel approach, 16 causal variants for hearing loss were identified, with 8 of them being previously unreported.
Article
Peripheral Vascular Disease
Xiqi Li, Aleksandar Milosavljevic, Sarah H. Elsea, Chi Chiu Wang, Fernando Scaglia, Argyro Syngelaki, Kypros H. Nicolaides, Liona C. Poon
Summary: Untargeted metabolomics analysis of plasma samples from high-risk pregnant women before and after aspirin treatment revealed metabolic effects of aspirin and differences potentially associated with treatment response. Aspirin treatment significantly reduces the rate of preterm preeclampsia in high-risk women and the treatment response is significantly linked to internal aspirin exposure levels.
Article
Clinical Neurology
Pouneh Amir Yazdani, Marie-Lou St-Jean, Sara Matovic, Aaron Spahr, Luan T. Tran, Renee-Myriam Boucher, Chantal Poulin, Bradley Osterman, Myriam Srour, Bernard Rosenblatt, Sebastien Chenier, Jean-Francois Soucy, Anne-Marie Laberge, Nancy Braverman, Maria Daniela D'Agostino, Cam-Tu Emilie Nguyen, Maxime Morsa, Genevieve Bernard
Summary: This study explored the experience of parents of children with genetically determined leukoencephalopathies during the COVID-19 pandemic. The results showed that parents experience a higher level of stress due to the shortage of health care services and the vulnerability of their children. Additionally, parents had a positive response to telemedicine and wished to continue using it after the pandemic.
JOURNAL OF CHILD NEUROLOGY
(2022)
Article
Clinical Neurology
Kirt Martin, Alice McConnell, Sarah H. Elsea
Summary: Pathogenic variants in the ALDH5A1 gene lead to SSADH deficiency, with an estimated global prevalence of 1/460,000 and highest carrier frequencies in East Asian and South Asian populations. However, the pan-ethnic carrier frequency for SSADH deficiency may not be fully represented in gnomAD, requiring further analysis to assess the prevalence of this ultra-rare disease.
JOURNAL OF CHILD NEUROLOGY
(2021)
Article
Genetics & Heredity
Julia Macintosh, Alexa Derksen, Chantal Poulin, Nancy Braverman, Adeline Vanderver, Isabelle Thiffault, Steffen Albrecht, Genevieve Bernard
Summary: This study reports an individual with NRROS variants presenting with a severe neurodegenerative phenotype, with pathological examination revealing extensive grey and white matter involvement, as well as abnormal mitochondrial ultrastructure.
Article
Genetics & Heredity
Anthony Cheung, Catherine Argyriou, Christine Yergeau, Yasmin D'Souza, Emilie Riou, Sebastien Levesque, Gerald Raymond, Mebratu Daba, Irakli Rtskhiladze, Tinatin Tkemaladze, Laura Adang, Roberta La Piana, Genevieve Bernard, Nancy Braverman
Summary: This study reviewed the medical records and brain MRIs of 7 patients with PEX16 phenotype, revealing that these patients exhibited some atypical features such as spasticity, cerebellar dysfunction, and prolonged survival. The study also identified novel clinical, neuroradiological, and molecular features of PEX16 defects and proposed a potential treatment for dystonia.
Article
Genetics & Heredity
Giavanna Verdi, Dong Li, Sarah H. Elsea, Beverly Nelson, Elizabeth J. Bhoj, Hakon Hakonarson, Katherine R. Yearwood, Sharmila Upadhya, Sarah Gluschitz, Janice L. Smith, Andrew K. Sobering
Summary: Through international collaboration, we identified a chromosomal abnormality in a boy of Afro-Caribbean descent. The clinical features of this boy suggest the presence of both partial deletion of chromosome 18 and partial duplication of chromosome 5, a combination that has not been described previously.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Geetali Pradhan, Jong Han Lee, Chia-Shan Wu, Hongying Wang, Ligen Lin, Taraka Donti, Brett H. Graham, Arun S. Rajan, Ashok Balasubramanyam, Susan L. Samson, Shaodong Guo, Yuxiang Sun
Summary: This study investigated the role of the Ghrelin receptor (GHS-R) in glucose-stimulated insulin secretion (GSIS) and its interaction with the insulin signaling pathway in pancreatic islets. The findings suggest that GHS-R affects key components of the insulin signaling pathway, likely regulating GSIS via the Akt-Pdx1-GLUT2 pathway.
Review
Cell Biology
Mousumi Bose, Christine Yergeau, Yasmin D'Souza, David D. Cuthbertson, Melisa J. Lopez, Alyssa K. Smolen, Nancy E. Braverman
Summary: Zellweger spectrum disorder (ZSD) is a rare genetic disorder that affects multiple organ systems and has broad clinical heterogeneity. This study aimed to determine if the characterization of clinical findings can predict severity in ZSD. The results showed significant differences in certain clinical findings across severity categories, including seizures, hypotonia, reduced mobility, feeding difficulties, renal cysts, adrenal insufficiency, hearing and vision loss, and shortened lifespan. The findings provide important information for determining appropriate outcomes in clinical trials for ZSD.
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
Psychology, Developmental
Anusha Gandhi, Dihong Zhou, Joseph Alaimo, Edwin Chon, Michael D. Fountain, Sarah H. Elsea
Summary: Caregivers of children with Smith-Magenis syndrome (SMS), MBD5-associated neurodevelopmental disorder (MAND), and Pitt-Hopkins syndrome (PTHS) were surveyed to assess sleep disturbance and identify specific sleep problems for each disorder. Results showed differences in sleep patterns compared to children with autism spectrum disorder (ASD), with PTHS having significant but less severe sleep disturbances than SMS and MAND. More support, education, and ongoing management of sleep are needed for these individuals due to the complexity of these conditions and challenges of underlying sleep disturbance.
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
(2021)
Article
Genetics & Heredity
Katerina S. Kucera, Beth Lincoln Boyea, Brooke Migliore, Sarah Nelson Potter, Veronica R. Robles, Oksana Kutsa, Heidi Cope, Katherine C. Okoniewski, Anne Wheeler, Catherine W. Rehder, Edward C. Smith, Holly L. Peay
Summary: Screening for elevated CK-MM levels in dried blood spots is a feasible method to identify newborns with DMD. Including specific cutoffs, repeat testing, and genetic sequencing can improve the accuracy and sensitivity of screening.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Madeline Currey, Ilana Solomon, Sarah Mcgraw, Jenny Shen, Francisco Munoz, Ernesto Sosa, Vanessa Puello-Lozano, Sam Wing, Lisa Lopez, Michelle Afkhami, Janine Lobello, Szabolcs Szelinger, Stacy W. Gray
Summary: This study conducted qualitative interviews with cancer patients and providers to identify gaps in clinical care and propose care delivery solutions for the return of secondary germline findings. The responses of patients varied depending on the amount of pre-test counseling they received, and providers identified insufficient clinic time as a major barrier to pretest education. Online support tools and standardized pre-test education models were favored by providers. There were differing perspectives on how pre-test education should be integrated into clinical workflows, but agreement on the inclusion of differences between somatic and germline testing, likelihood of medically actionable findings, and the possibility of being referred to a genetics provider.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kiely N. James, Shimul Chowdhury, Yan Ding, Sergey Batalov, Kelly Watkins, Yong Hyun Kwon, Lucitia Van Der Kraan, Katarzyna Ellsworth, Stephen F. Kingsmore, Lucia Guidugli
Summary: This study used genome sequencing to detect a wide range of copy-number variants (CNVs) and other non-single nucleotide variant/indel variant types. These genetic alterations accounted for 15.8% of reported variants, with deletions being the most common type. The study also found that additional genetic tests were ordered in some cases, but failed to report the variants detected by genome sequencing.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Asem Berkalieva, Nicole R. Kelly, Ashley Fisher, Samuel F. Hohmann, Monisha Sebastin, Miranda Di Biase, Katherine E. Bonini, Priya Marathe, Jacqueline A. Odgis, Sabrina A. Suckiel, Michelle A. Ramos, Rosamond Rhodes, Noura S. Abul-Husn, John M. Greally, Carol R. Horowitz, Melissa P. Wasserstein, Eimear E. Kenny, Bruce D. Gelb, Bart S. Ferket
Summary: The study aims to understand the effects of returning diagnostic sequencing results on clinical actions and economic outcomes for pediatric patients with suspected genetic disorders. The results showed that patients with positive findings were more likely to receive specialist consultation, but there were no significant increases in overall physician services and costs. More large-scale studies are needed to confirm these findings.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kirstine Stochholm, Camilla Holmgard, Shanlee M. Davis, Claus H. Gravholt, Agnethe Berglund
Summary: This study assessed the incidence, prevalence, and age at diagnosis of individuals with 45,X/46,XY mosaicism and described the associated mortality pattern. The study found an increasing incidence of 45,X/46,XY mosaicism in males and a stable incidence in females. Males were diagnosed at an older age than females. Additionally, 45,X/46,XY mosaicism was associated with increased all-cause mortality.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Yunjia Chen, Ender Karaca, Nathaniel H. Robin, Dana Goodloe, Ali Al-Beshri, S. Joy Dean, Anna C. E. Hurst, Andrew J. Carroll, Fady M. Mikhail
Summary: This study confirms the association between DLG2 intragenic deletions and neurodevelopmental disorders, supports the haploinsufficiency of the DLG2 gene, and suggests a potential association between these deletions and congenital anomalies and dysmorphism.
GENETICS IN MEDICINE
(2024)
