Review
Genetics & Heredity
Pitcha Chompoopong, Margherita Milone
Summary: GDP-mannose pyrophosphorylase B (GMPPB) is a cytoplasmic protein that catalyzes the formation of GDP-mannose. Impaired GMPPB function leads to alpha-dystroglycan (alpha-DG) disruptions, causing dystroglycanopathy. GMPPB-related disorders are inherited in an autosomal recessive manner and can manifest as severe congenital muscular dystrophy (CMD), limb-girdle muscular dystrophy (LGMD), or recurrent rhabdomyolysis. Mutations in GMPPB can also affect neuromuscular transmission and cause congenital myasthenic syndrome. The unique feature of GMPPB-related disorders is the impairment of neuromuscular transmission.
Article
Biochemistry & Molecular Biology
Rebeka Kodrikova, Zuzana Pakanova, Maros Krchnak, Maria Sediva, Sergej Sestak, Filip Kveton, Gabor Beke, Anna Salingova, Katarina Skalicka, Katarina Brennerova, Emilia Jancova, Peter Barath, Jan Mucha, Marek Nemcovic
Summary: In this study, a male patient with a novel missense variant in the SLC35A2 gene was analyzed for glycoprofile. Abnormal serum N-glycoprofile with increased levels of agalactosylated and monogalactosylated N-glycans was observed. Whole exome sequencing and Sanger sequencing revealed a new mutation in the SLC35A2 gene. Distinctive N-glycan biomarkers were characterized by combining biochemical, analytical, and genomic approaches.
Article
Medicine, General & Internal
Mi Yang, Ru-Xin Xing
Summary: Congenital muscular dystrophy (CMD) is a genetically heterogeneous group of muscle disorders. This study identified CRPPA gene mutations in a Chinese family, expanding the clinical and mutational spectrum of CMD associated with CRPPA mutations. The proband had a homozygous deletion while the parents had a heterozygous deletion without symptoms.
WORLD JOURNAL OF CLINICAL CASES
(2021)
Article
Genetics & Heredity
Nazreen Kamarus Jaman, Preeya Rehsi, Robert H. Henderson, Ulrike Loebel, Kshitij Mankad, Stephanie Grunewald
Summary: The key diagnostic features of SRD5A3-CDG include early-onset ophthalmological problems such as retinal dystrophy and optic nerve hypoplasia. The condition is also characterized by variable neurological symptoms, including intellectual disability, ataxia, and hypotonia. Other findings in this study include skin lesions, joint laxity, and scoliosis, as well as additional symptoms like dystonia, anxiety disorder, and gastrointestinal issues.ródzenia.
FRONTIERS IN GENETICS
(2021)
Article
Medical Laboratory Technology
Antoine Civit, Paul Gueguen, Helene Blasco, Isabelle Benz-de-Bretagne, Elodie Lebredonchel, Giulia Dingeo, Mederic Jeanne, Sophie Rouxel, Marine Tardieu, Alexandre Raynor, Francois Labarthe, Arnaud Bruneel, Violette Goetz
Summary: This case report describes a newborn male with obstructive hydrocephalus caused by bilateral cerebellar hemorrhage and later developed fulminant hepatitis. Initial screenings for congenital disorder of glycosylation (CDG) suggested mannose-phosphate isomerase deficiency, but further genetic analysis revealed a pathogenic variant in ALDOB, indicating hereditary fructose intolerance (HFI).
CLINICA CHIMICA ACTA
(2023)
Review
Genetics & Heredity
Hanna Lausmann, Martin Zacharias, Teresa M. Neuhann, Melanie K. Locher, Karl F. Schettler
Summary: This study reported a case of DPM1-CDG in a very young and severely affected child. Through genetic sequencing and protein structure simulation, it was found that the deletion of Lys80 in the DPM1 gene may result in abnormal protein structure. This has implications for further understanding the function and structure of DPM1.
FRONTIERS IN GENETICS
(2022)
Article
Medicine, Research & Experimental
Rene G. Feichtinger, Andreas Huellen, Andreas Koller, Dieter Kotzot, Valerian Grote, Erdmann Rapp, Peter Hofbauer, Karin Brugger, Christian Thiel, Johannes A. Mayr, Saskia B. Wortmann
Summary: GFUS-CDG is a genetic disorder that can be improved by supplementing with L-fucose.
EMBO MOLECULAR MEDICINE
(2021)
Article
Genetics & Heredity
Farhana Taher Sumya, Irina D. Pokrovskaya, Vladimir Lupashin
Summary: Researchers successfully developed cellular models for COG4 mutations in RPE1 and HEK293T cell lines, thoroughly characterizing them using various methods and revealing specific defects in glycosylation and protein secretion in mutant cells. The study suggests that cellular models with COG mutations may aid in further investigating the molecular mechanisms of the disease and potentially provide guidance for the treatment of COG-CDGs.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Roberta Salinas-Marin, Yoshiko Murakami, Carlos Alberto Gonzalez-Dominguez, Mario Ernesto Cruz-Munoz, Hector Manuel Mora-Montes, Eva Morava, Taroh Kinoshita, Susana Monroy-Santoyo, Ivan Martinez-Duncker
Summary: A case of PIGA-CDG was reported in Mexico, with a male child presenting neurological and gastrointestinal symptoms, including megacolon. Exome sequencing identified a variant in the PIGA gene, which was characterized as pathogenic through functional experiments.
FRONTIERS IN GENETICS
(2022)
Review
Pediatrics
Siliang Lu, Shuheng Liang, Yi Wu, Jinyi Liu, Lin Lin, Guosheng Huang, Huaijun Ning
Summary: We report a case of a 2-year-old girl diagnosed with Mannose-6-phosphate isomerase-congenital disorder of glycosylation (MPI-CDG) and provide a literature review. The patient had compound heterozygous mutations in the MPI gene, with one mutation inherited from the mother and another from the father. After mannose treatment, the symptoms of vomiting and diarrhea disappeared completely and no side effects were observed. Our findings suggest that MPI-CDG should be considered in children with unexplained recurrent digestive and endocrine systems involvement, and gene examination should be performed for a timely diagnosis and treatment initiation.
FRONTIERS IN PEDIATRICS
(2023)
Article
Cell Biology
Zoe Durin, Marine Houdou, Willy Morelle, Lydia Barre, Aurore Layotte, Dominique Legrand, Mohamed Ouzzine, Francois Foulquier
Summary: Glycosylation is a universal cellular process that can lead to severe genetic diseases. Oral D-Galactose therapy shows promise in treating specific CDG, while MnCl2 supplementation can fully rescue glycosylation defects caused by TMEM165 deficiency. However, D-Galactose only affects N-linked glycosylation while MnCl2 supplementation rescues all glycosylation types.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Genetics & Heredity
Milena Greczan, Dariusz Rokicki, Dorota Wesol-Kucharska, Magdalena Kaczor, Agata Rawiak, Aleksandra Jezela-Stanek
Summary: The aim of this study is to describe the perinatal phenotype of congenital disorders of N-glycosylation. The study findings indicate that the presence of certain distinctive combinations of symptoms in the perinatal period should raise suspicion of CDGs.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Sander Pajusalu, Mari-Anne Vals, Laura Mihkla, Ustina Samarina, Tiina Kahre, Katrin Ounap
Summary: This study aimed to analyze the estimated prevalence of different N-linked protein glycosylation disorders, using data from diverse populations and databases. While PMM2-CDG was found to have the highest prevalence, the research also highlighted variations in prevalence across different populations, providing valuable guidance for CDG research and clinical care.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Van Khanh Tran, Ngoc-Lan Nguyen, Lan Ngoc Thi Tran, Phuong Thi Le, Anh Hai Tran, Tuan L. A. Pham, Nguyen Thi Kim Lien, Nguyen Thi Xuan, Le Tat Thanh, Thanh Van Ta, Thinh Huy Tran, Huy-Hoang Nguyen
Summary: This study identified seven pathogenic/likely pathogenic variants in the LAMA2 gene in six patients with congenital muscular dystrophy from five unrelated Vietnamese families, providing genetic etiology and counseling for their parents.
FRONTIERS IN GENETICS
(2023)
Article
Genetics & Heredity
P. A. Chausova, O. P. Ryzhkova, G. E. Rudenskaya, V. B. Chernykh, O. A. Shchagina, A. V. Polyakov
Summary: Merosine deficient congenital muscular dystrophy is a common form of muscular dystrophy caused by a genetic deficiency. New variants with this type of inheritance may be hidden in the genetic makeup of parents.
FRONTIERS IN GENETICS
(2021)
Editorial Material
Rheumatology
Ryan J. Diel, Claire E. Hannah, Steven A. Moore, Brittany Bettendorf
JCR-JOURNAL OF CLINICAL RHEUMATOLOGY
(2021)
Article
Clinical Neurology
Martin Rees, Roksana Nikoopour, Atsushi Fukuzawa, Ay Lin Kho, Miguel A. Fernandez-Garcia, Elizabeth Wraige, Istvan Bodi, Charu Deshpande, Oezkan Oezdemir, Hulya-Sevcan Daimagueler, Mark Pfuhl, Mark Holt, Birgit Brandmeier, Sarah Grover, Joel Fluss, Cheryl Longman, Maria Elena Farrugia, Emma Matthews, Michael Hanna, Francesco Muntoni, Anna Sarkozy, Rahul Phadke, Ros Quinlivan, Emily C. Oates, Rolf Schroeder, Christian Thiel, Jens Reimann, Nicol Voermans, Corrie Erasmus, Erik-Jan Kamsteeg, Chaminda Konersman, Carla Grosmann, Shane McKee, Sandya Tirupathi, Steven A. Moore, Ekkehard Wilichowski, Elke Hobbiebrunken, Gabriele Dekomien, Isabelle Richard, Peter Van den Bergh, Cristina Dominguez-Gonzalez, Sebahattin Cirak, Ana Ferreiro, Heinz Jungbluth, Mathias Gautel
Summary: The diagnosis of TTN-related myopathies can be complicated due to overlap with other myopathies and TTN variants in control populations. This study identified key clinical and pathological features that can suggest TTN-related myopathies, and demonstrated the destabilizing nature of missense mutations associated with CMs. These findings suggest a potential therapeutic target for recessive titinopathies.
ACTA NEUROPATHOLOGICA
(2021)
Letter
Oncology
Torin W. Waters, Steven A. Moore, Yutaka Sato, Brian J. Dlouhy, Mariko Sato
PEDIATRIC BLOOD & CANCER
(2021)
Article
Pathology
Aaron A. Stence, Jon G. Thomason, Jonathan A. Pruessner, Ramakrishna R. Sompallae, Anthony N. Snow, Deqin Ma, Steven A. Moore, Aaron D. Bossler
Summary: The study validated the use of optical genome mapping for FSHD analysis, showing it to be an accurate and highly reproducible method for chromosomal abnormalities associated with FSHD.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2021)
Article
Biochemistry & Molecular Biology
Sarah J. Smith, Lacramioara Fabian, Adeel Sheikh, Ramil Noche, Xiucheng Cui, Steven A. Moore, James J. Dowling
Summary: Congenital muscular dystrophy type 1A (MDC1A) is a common genetic disorder caused by mutations in the LAMA2 gene. In this study, researchers used a zebrafish model to investigate the role of lysosome distribution in MDC1A. They found that abnormal lysosome distribution was associated with fiber detachment and could be improved by overexpression of a transcription factor called transcription factor EB. This suggests that targeting lysosome function may be a potential therapeutic strategy for treating MDC1A.
HUMAN MOLECULAR GENETICS
(2022)
Article
Genetics & Heredity
Megan A. Waldrop, Steven A. Moore, Katherine D. Mathews, Benjamin W. Darbro, Livja Medne, Richard Finkel, Anne M. Connolly, Thomas O. Crawford, Daniel Drachman, Nicolas Wein, Ali A. Habib, Monika A. Krzesniak-Swinarska, Craig M. Zaidman, James J. Collins, Manu Jokela, Bjarne Udd, John W. Day, Gloria Ortiz-Guerrero, Jeff Statland, Russell J. Butterfield, Diane M. Dunn, Robert B. Weiss, Kevin M. Flanigan
Summary: Deep intronic DMD mutations can be identified through muscle RNA analysis, which is an important diagnostic step for patients with abnormal dystrophin expression but negative genomic testing results. This study identified three types of pathogenic pseudoexon mutations and proposed potential treatment approaches based on the mutation type.
Article
Clinical Neurology
Payam Mohassel, Ning Chang, Kaoru Inoue, Angela Delaney, Ying Hu, Sandra Donkervoort, Dimah Saade, B. Jeanne Billioux, Brooke Meader, Rita Volochayev, Chamindra G. Konersman, Angela M. Kaindl, Chie-Hee Cho, Bianca Russell, Adrian Rodriguez, K. Wade Foster, A. Reghan Foley, Steven A. Moore, Peter L. Jones, Carsten G. Bonnemann, Takako Jones, Natalie D. Shaw
Summary: In this study, we identified individuals with arhinia who met the genetic and epigenetic criteria for FSHD2 and showed molecular hallmark of FSHD-DUX4 derepression and expression in vitro, but did not have the typical clinical phenotype of FSHD2. This suggests the presence of novel disease-modifying factors that operate as a switch between FSHD2 and arhinia phenotypes.
Article
Neurosciences
Nicole Becker, Steven A. Moore, Karra A. Jones
Summary: The inflammatory histopathology of dysferlinopathy is more similar to limb-girdle pattern muscular dystrophies than true inflammatory myopathies. Dysferlinopathy muscle biopsies have minimal inflammatory cell infiltrates, absent to focal MHC class I expression, and diffuse myofiber complement C5b-9 deposition.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Takahiro Yonekawa, Adam J. Rauckhorst, Sara El-Hattab, Marco A. Cuellar, David Venzke, Mary E. Anderson, Hidehiko Okuma, Alvin D. Pewa, Eric B. Taylor, Kevin P. Campbell
Summary: In late stages of muscular dystrophy, systemic delivery of AAV2/9 CMV Large1 can restore muscle function, improve motor and respiratory function, and extend survival.
Article
Biochemistry & Molecular Biology
Anabel S. De La Garza-Rodea, Steven A. Moore, Jesus Zamora-Pineda, Eric P. Hoffman, Karishma Mistry, Ashok Kumar, Jonathan B. Strober, Piming Zhao, Jung H. Suh, Julie D. Saba
Summary: This study reveals that Duchenne muscular dystrophy (DMD) patients have increased expression of SPL and dysregulated S1P metabolism in skeletal muscles. Treatment with the SPL inhibitor LX2931 increases the number of muscle stem cells (SC), reduces leukocyte infiltration, and attenuates muscle inflammation and degeneration. The treatment also leads to changes in gene expression related to immune function, plasma membrane interactions, and axon guidance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
M. Osman Sheikh, Chantelle J. Capicciotti, Lin Liu, Jeremy Praissman, Dahai Ding, Daniel G. Mead, Melinda A. Brindley, Tobias Willer, Kevin P. Campbell, Kelley W. Moremen, Lance Wells, Geert-Jan Boons
Summary: Matriglycan plays a critical role in protein binding and viral infection, and its length can be adjusted accordingly. This finding contributes to a better understanding of the interaction between cells and viruses.
NATURE COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Catherine I. Soderstrom, Jennifer Larsen, Carolina Owen, David Gifondorwa, David Beidler, Florence H. Yong, Patricia Conrad, Hendrik Neubert, Steven A. Moore, Mohamed Hassanein
Summary: Duchenne muscular dystrophy (DMD) is a degenerative muscular disease with no cure. New advances in gene therapy and understanding of the disease have opened up new treatment opportunities. This article describes a novel Western blot method for monitoring dystrophin expression and assessing treatment efficacy.
Article
Medicine, General & Internal
Arnold H. H. Menezes, Yutaka Sato, Brian J. J. Dlouhy, Karra A. A. Jones, Steven A. A. Moore
Summary: A Caucasian female neonate with ventriculus terminalis cyst, extra-axial conofilar cyst, and tethered lipomatous filum underwent surgical intervention due to progressive cyst enlargement. The cyst was excised and the lipomatous filum was sectioned during the surgery. The child had a good recovery without deficits at 4-year follow up.
JOURNAL OF MEDICAL CASE REPORTS
(2023)
Article
Multidisciplinary Sciences
Kaoru Inoue, Hamed Bostan, MaKenna R. Browne, Owen F. Bevis, Carl D. Bortner, Steven A. Moore, Aaron A. Stence, Negin P. Martin, Shih-Heng Chen, Adam B. Burkholder, Jian-Liang Li, Natalie D. Shaw
Summary: SMCHD1 mutations cause congenital arhinia and FSHD2. Loss of SMCHD1 activity leads to DUX4 expression and cell death in placode cells derived from hESCs and iPSCs. Herpesvirus infection may amplify DUX4 expression in SMCHD1 KO cells, indicating an environmental disease modifier.
Article
Cell Biology
Agathe Marcelot, Felipe Rodriguez-Tirado, Philippe Cuniasse, Mei-ling Joiner, Simona Miron, Alexey A. Soshnev, Mimi Fang, Miles A. Pufall, Katherine D. Mathews, Steven A. Moore, Sophie Zinn-Justin, Pamela K. Geyer
Summary: Barrier-to-autointegration factor (BAF) is an essential component of the nuclear lamina that regulates gene expression, cell cycle progression, and nuclear integrity. A dominant pathogenic BAF variant, Gly16Arg, has been identified in a patient with progressive neuromuscular weakness, causing changes in chromatin structure and nuclear functions. This study demonstrates how a missense mutation can alter protein conformation and lead to a dominant disease phenotype.