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
Clinical Neurology
Susana Quijano-Roy, Jana Haberlova, Claudia Castiglioni, John Vissing, Francina Munell, Francois Rivier, Tanya Stojkovic, Edoardo Malfatti, Marta Gomez Garcia de la Banda, Giorgio Tasca, Laura Costa Comellas, Audrey Benezit, Helge Amthor, Ivana Dabaj, Clara Gontijo Camelo, Pascal Laforet, John Rendu, Norma B. Romero, Eliana Cavassa, Fabiana Fattori, Christophe Beroud, Jana Zidkova, Nicolas Leboucq, Nicoline Lokken, Angel Sanchez-Montanez, Ximena Ortega, Martin Kyncl, Corinne Metay, David Gomez-Andres, Robert Y. Carlier
Summary: Patients with LAMA2-RD exhibit a consistent pattern of abnormal muscle fat replacement in muscle imaging, which serves as a supportive diagnostic tool. Thigh muscles appear to be the most informative for assessing disease progression.
JOURNAL OF NEUROLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Enrico Bugiardini, Andreia M. Nunes, Ariany Oliveira-Santos, Marisela Dagda, Tatiana M. Fontelonga, Pamela Barraza-Flores, Alan M. Pittman, Jasper M. Morrow, Matthew Parton, Henry Houlden, Perry M. Elliott, Petros Syrris, Roderick P. Maas, Mohammed M. Akhtar, Benno Kusters, Joost Raaphorst, Meyke Schouten, Erik-Jan Kamsteeg, Baziel van Engelen, Michael G. Hanna, Rahul Phadke, Luis R. Lopes, Emma Matthews, Dean J. Burkin
Summary: This study describes the pathological changes caused by ITGA7 mutations in skeletal and cardiac muscle. Patients exhibited cardiac dysfunction and respiratory insufficiency, and mouse experiments also showed abnormalities related to the heart and muscles. The results suggest a critical role for integrin alpha 7 beta 1 in cardiac function.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Clinical Neurology
Hossam M. Sakr, Nagia Fahmy, Nermine S. Elsayed, Hala Abdulhady, Tamer A. El-Sobky, Amr M. Saadawy, Christophe Beroud, Bjarne Udd
Summary: This study analyzed the pattern of muscle involvement in children with merosin-deficient CMD using whole-body muscle MRI. The results showed a consistent pattern of muscle fatty infiltration in the patient group compared to the control group, with specific differences in various muscle groups. These findings suggest that whole-body muscle MRI can be a valuable tool in the differential diagnosis of children with merosin-deficient CMD.
NEUROMUSCULAR DISORDERS
(2021)
Review
Clinical Neurology
Andrea Salvati, Eleonora Bonaventura, Gianluca Sesso, Rossella Pasquariello, Federico Sicca
Summary: Epilepsy is a common feature of LAMA2-RD, with an average age of onset around 8 years old. The onset age varies significantly between early and late-onset disease, as well as between complete and partial merosin deficiency.
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
(2021)
Article
Genetics & Heredity
Natalia Diaz-Lombana, Lorena Diaz-Ordonez, Juan David Gutierrez-Medina, Harry Pachajoa
Summary: CMD1A is a rare autosomal recessive disorder caused by mutations in the LAMA2 gene. This article describes the first genetically confirmed case of CMD1A in Colombia, with a novel variant causing the disease. The patient exhibited typical clinical features of CMD1A, including peripheral hypotonia, muscle weakness, and elevated CPK levels, and underwent corrective surgeries for severe scoliosis and feeding difficulties.
FRONTIERS IN GENETICS
(2023)
Article
Cell Biology
Ariany Oliveira-Santos, Marisela Dagda, Jennifer Wittmann, Robert Smalley, Dean J. Burkin
Summary: LAMA2-CMD is a neuromuscular disease caused by mutations in the LAMA2 gene, leading to the loss of laminin-211/221 heterotrimers in skeletal muscle. Patients exhibit severe hypotonia and progressive muscle weakness, with no effective treatment currently available. The loss of laminin-alpha 2 results in muscle degeneration, defective muscle repair, and dysregulation of multiple signaling pathways. Vemurafenib, a serine/threonine kinase inhibitor, was found to partially restore signaling pathways and improve histopathology in a mouse model of LAMA2-CMD, but did not improve muscle function.
DISEASE MODELS & MECHANISMS
(2023)
Article
Clinical Neurology
Stefanie Meyer, Silke Kaulfuss, Sabrina Zechel, Karsten Kummer, Ali Seif Amir Hosseini, Marielle Sophie Ernst, Jens Schmidt, Silke Pauli, Jana Zschuentzsch
Summary: This study presents a diagnostic approach for clinically suspected hereditary muscular dystrophy by combining advanced Next Generation Sequencing with thorough phenotype assessment. It demonstrates the challenges in interpreting variants of unknown significance and highlights the importance of individualized diagnostic procedures in accurate diagnosis.
FRONTIERS IN NEUROLOGY
(2022)
Review
Clinical Neurology
Clara Gontijo Camelo, Mariana Cunha Artilheiro, Cristiane Araujo Martins Moreno, Suely Fazio Ferraciolli, Andre Macedo Serafim Silva, Tatiana Ribeiro Fernandes, Leandro Tavares Lucato, Antonio Jose Rocha, Umbertina Conti Reed, Edmar Zanoteli
Summary: This observational study describes the frequency of cortical malformations, epilepsy, and intellectual disability in a Brazilian cohort of LAMA2-RD patients and correlates these neurological findings with genetic and motor function. The results show that these manifestations are more common than previously reported and are correlated with the severity of motor function and the presence of variants affecting the laminin-alpha 2 LG domain.
JOURNAL OF NEUROMUSCULAR DISEASES
(2023)
Article
Medical Laboratory Technology
Afshin Khorrami, Pouya Goleij, Vahidreza Karamad, Elham Taheri, Behrouz Shadman, Parisa Emami, Gholamreza Jahangirzadeh, Saba Hajazimian, Alireza Isazadeh, Behzad Baradaran, Mansour Heidari
Summary: Overall, we identified two potentially pathogenic missense mutations in compound heterozygous state in the LAMA2 gene in an Iranian patient with MDC1A using WES. The identified mutations can be beneficial for genetic counseling, prenatal diagnosis, and predicting the prognosis of MDC1A.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2021)
Review
Clinical Neurology
Duo-Zi Wang, Bing-Hu Li, Qiong Ma, Zhou Yu, Kai Chen, Ying He, Song Tan
Summary: This article reports a case of a 52-year-old woman with rare limb-girdle muscular dystrophy (LGMDR23), characterized by proximal weakness in the limbs. Magnetic resonance imaging (MRI) showed symmetrical sphenoid wings-like white matter demyelination in bilateral lateral ventricles. Electromyography revealed quadriceps muscle damage in both lower extremities. Next-generation sequencing (NGS) identified two loci variations in the LAMA2 gene. This case highlights the importance of considering LGMDR23 in patients with weakness and white matter demyelination on MRI brain, and expands the gene variants spectrum of LGMDR23.
FRONTIERS IN NEUROLOGY
(2023)
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
Medicine, Research & Experimental
Sandra Donkervoort, Niklas Krause, Mykola Dergai, Pomi Yun, Judith Koliwer, Svetlana Gorokhova, Janelle Geist Hauserman, Beryl B. Cummings, Ying Hu, Rosemarie Smith, Prech Uapinyoying, Vijay S. Ganesh, Partha S. Ghosh, Kristin G. Monaghan, Seby L. Edassery, Pia E. Ferle, Sarah Silverstein, Katherine R. Chao, Molly Snyder, Sara Ellingwood, Diana Bharucha-Goebel, Susan T. Iannaccone, Matteo Dal Peraro, A. Reghan Foley, Jeffrey N. Savas, Veronique Bolduc, Dirk Fasshauer, Carsten G. Bonnemann, Michael Schwake
Summary: This study identifies BET1 as a novel gene associated with severe congenital muscular dystrophy (CMD) and epilepsy, revealing its role in protein transport and interaction with other partners. The variant p.(Ile51Ser) is found to affect BET1 protein binding and interaction with proteins like ERGIC-53. The findings support the emerging role of ER/Golgi SNAREs in CMD and shed light on potential mechanisms underlying these diseases.
EMBO MOLECULAR MEDICINE
(2021)
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)
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)
Letter
Clinical Neurology
Joao Moura, Ana Sardoeira, Jorge Oliveira, Alexandre Mendes, Jose Barros, Jorge Sequeiros, Clara Barbot, Joana Damasio
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2023)
Article
Genetics & Heredity
Nuno Maia, Nekane Ibarluzea, Mala Misra-Isrie, Daniel C. Koboldt, Isabel Marques, Gabriela Soares, Rosario Santos, Carlo L. M. Marcelis, Riikka Keski-Filppula, Miriam Guitart, Elisabeth Gabau Vila, April Lehman, Scott Hickey, Mari Mori, Paulien Terhal, Irene Valenzuela, Amaia Lasa-Aranzasti, Anna Maria Cueto-Gonzalez, Brian H. Chhouk, Rebecca C. Yeh, Jennifer E. Neil, Bassam Abu-Libde, Tjitske Kleefstra, Mariet W. Elting, Andrea Csaszar, Judit Karteszi, Beata Bessenyei, Hans van Bokhoven, Paula Jorge, Johanna M. van Hagen, Arjan P. M. de Brouwer
Summary: We described the phenotype of 22 male patients (20 probands) with a hemizygous missense variant in the MED12 gene. The phenotypic spectrum ranges from nonspecific intellectual disability to well-known syndromes. The identified variants were randomly distributed throughout the gene but mostly outside the functional domains. Statistical analyses did not show a correlation between the MED12-related phenotypes and the locations of the variants or the protein domain involved. In conclusion, establishing a genotype-phenotype correlation in MED12-related diseases remains challenging, and patients with a causative MED12 variant may be underdiagnosed due to their diverse clinical presentations.
Rating: 9/10
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Correction
Medicine, General & Internal
Teresinha Evangelista, Malick Kandji, Emmanuelle Lacene, Anais Chanut, Mai Thao Bui, Rudy Marty, Laurent Buffat, Kenneth Knoblauch, Brian B. Rudkin, Norma Beatriz Romero
Letter
Medicine, General & Internal
Filipe R. Pinto, Antonio Lamas, Daniel G. Oliveira, Marcia E. Oliveira, Raquel Faria
ACTA MEDICA PORTUGUESA
(2023)
Article
Genetics & Heredity
R. Pereira, V. Carvalho, C. Dias, T. Barbosa, J. Oliveira, A. Alves, E. Oliveira, R. Sa, M. Sousa
Summary: This study presents a case of a female patient with primary ciliary dyskinesia (PCD) and infertility. The patient's twin sister also has PCD and infertility. Through various assessments, such as cilia motility evaluation, axoneme ultrastructure observation, and genetic characterization, a homozygous nonsense variant in the DRC1 gene was identified as the cause of PCD and infertility in the patient.
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
(2023)
Letter
Clinical Neurology
Joana Damasio, Clara Barbot, Rui Felgueiras, Ana Filipa Brandao, Jose Barros, Jorge Oliveira, Jorge Sequeiros
MOVEMENT DISORDERS
(2023)
Review
Clinical Neurology
Bhaskar Roy, Allison Peck, Teresinha Evangelista, Gerald Pfeffer, Leo Wang, Jordi Diaz-Manera, Manisha Korb, Matthew P. Wicklund, Margherita Milone, Miriam Freimer, Hani Kushlaf, Rocio-Nur Villar-Quiles, Tanya Stojkovic, Merrilee Needham, Johanna Palmio, Thomas P. Lloyd, Benison Keung, Tahseen Mozaffar, Conrad Chris Weihl, Virginia Kimonis
Summary: Valosin-containing protein (VCP)-associated multisystem proteinopathy (MSP) is a rare genetic disorder that affects the autophagy pathway, leading to myopathy, bone diseases, and neurodegeneration. There is currently no consensus-based guideline for the treatment of VCP myopathy. An initiative by Cure VCP Disease Inc. has developed a set of provisional recommendations for the management of VCP myopathy through online surveys, literature review, and expert consultations.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Susana Coimbra, Cristina Catarino, Maria Sameiro Faria, Jose Pedro L. Nunes, Susana Rocha, Maria Joao Valente, Petronila Rocha-Pereira, Elsa Bronze-da-Rocha, Nuno Bettencourt, Ana Beco, Sofia Homem de Melo Marques, Jose Gerardo Oliveira, Jose Madureira, Joao Carlos Fernandes, Vasco Miranda, Luis Belo, Alice Santos-Silva
Summary: Left ventricular hypertrophy (LVH) is common in end-stage kidney disease (ESKD) patients, and is associated with lower leptin levels, higher biomarkers of myocardial stress/injury, and specific nutritional status. Leptin and NT-proBNP are independent determinants of LVH, while dialysis vintage, hemoglobin, calcium, NT-proBNP, and leptin are predictive markers for LVH development. Further studies are needed to elucidate the role of leptin in LVH in ESKD patients.
Editorial Material
Clinical Neurology
Joana Fonte, Celia Machado, Jorge Oliveira, Marina Magalhaes
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Review
Clinical Neurology
Maria Joao Malaquias, Jorge Oliveira, Manuela Santos, Ana Filipa Brandao, Ana Sardoeira, Jorge Sequeiros, Jose Barros, Joana Damasio
Summary: This case study describes a family with two consecutive generations affected by Friedreich ataxia (FA), a rare autosomal recessive disorder. All five patients in the family had biallelic (GAA)(n) expansions in the FXN gene. Pseudodominance, a phenomenon observed in several neurological disorders, including those with high carrier frequencies, should be considered by clinicians when facing an apparently autosomal dominant pedigree.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Genetics & Heredity
Mariana Santos, Joao Massano, Alexandra Manuel Lopes, Ana Filipa Brandao, Joao Parente Freixo, Jorge Oliveira
Summary: In this report, we identified a novel heterozygous splice-site variant in VPS16 in a patient with cervical and upper limb dystonia, and analyzed the disruption of exon 3/intron 3 donor splice-site at the mRNA level, resulting in a frameshift mutation. Our report contributes with the first fully characterized variant of splice-affecting VPS16-related dystonia at the mRNA level.
Letter
Medicine, General & Internal
Filipe R. Pinto, Antonio Lamas, Daniel G. Oliveira, Marcia E. Oliveira, Raquel Faria
ACTA MEDICA PORTUGUESA
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Sara Morais, Ana Filipa Brandao, Ana Lopes, Rita Bastos-Ferreira, Susana Sousa, Paulo Silva, Fatima Lopes, Alexandra Lopes, Joana Damasio, Jose Leal Loureiro, Marina Magalhaes, Miguel Leao, Cristina Costa, Ricardo Mare, Jorge Sequeiros, Joao Parente Freixo, Jorge Oliveira
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Ana Filipa Brandao, Sara Morais, Rita Bastos-Ferreira, Susana Sousa, Marina Magalhaes, Antonio Bastos Lima, Jose Alves Grilo Goncalves, Leonor Correia Guedes, Alexandre Mendes, Ana Graca Velon, Carlos Sanchez Bueno, Joao Proenca, Maria Manuela Manuela Costa, Ana Oliveira, Joaquim Ferreira, Mario Romero Blanco, Rui Araujo, Tania Lampreia, Joao Parente Freixo, Jorge Sequeiros, Jorge Oliveira
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Fernanda Fortunato, Marianna Farne, Francesca Bianchi, Marcella Neri, Gabriele Siciliano, Valeria Sansone, Andrea Barp, Emilio Albamonte, Gianluca Vita, Antonio Atalaia, Teresinha Evangelista, Francesca Gualandi, Alessandra Ferlini
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)