Review
Medicine, General & Internal
Camille Bouchard, Jacques P. Tremblay
Summary: This review article presents 39 genes associated with limb-girdle muscular dystrophies (LGMDs), which can be inherited dominantly or recessively. The classification of LGMDs has evolved over time and now requires a mutation causing proximal muscle weakness found in multiple unrelated families. The article also discusses available and developing therapies for LGMDs, aiming to address the root cause of the disease instead of treating individual symptoms.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Clinical Neurology
Eric M. Libell, Noelle C. Bowdler, Carrie M. Stephan, Miriam Bridget Zimmerman, Amber M. Gedlinske, Katherine D. Mathews
Summary: This study investigated the experiences and outcomes of pregnancy in women with LGMDR9, finding that most pregnancies were uncomplicated but may require assisted vaginal delivery and could lead to progression of weakness. More research on pregnancy in specific LGMD subtypes is needed to confirm these findings and determine if risks vary by genotype.
Article
Clinical Neurology
Martin Krenn, Matthias Tomschik, Matias Wagner, Gudrun Zulehner, Rosa Weng, Jakob Rath, Sigrid Klotz, Ellen Gelpi, Gabriel Bsteh, Omar Keritam, Isabella Colonna, Chiara Paternostro, Fiona Jaeger, Elisabeth Lindeck-Pozza, Stephan Iglseder, Susanne Grinzinger, Martina Schoenfelder, Christina Hohenwarter, Manfred Freimueller, Norbert Embacher, Julia Wanschitz, Raffi Topakian, Ana Toepf, Volker Straub, Stefan Quasthoff, Fritz Zimprich, Wolfgang N. Loescher, Hakan Cetin
Summary: The study focused on hereditary myopathies with limb-girdle muscular weakness (LGW) and found that using next-generation sequencing (NGS) earlier in the diagnostic process is necessary to avoid long delays in diagnosis. Parameters predictive of a molecular diagnosis were identified, which can help select patients for genetic analyses, especially in centers with limited access to sequencing technology.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Genetics & Heredity
Jose Luis Garcia-Gimenez, Elena R. Garcia-Trevijano, Ana Aviles-Alia, Jose Santiago Ibanez-Cabellos, Miquel Bovea-Marco, Teresa Bas, Federico Pallardo, Juan R. Vina, Rosa Zaragoza
Summary: This study identified a potential molecular signature consisting of circulating miR-122-5p/miR-192-5p/miR-323-3p and biochemical parameters that could be used for prognosis and stratification of patients with limb-girdle muscular dystrophy (LGMD).
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Chemistry, Medicinal
Lizzia Raffaghello, Elisa Principi, Serena Baratto, Chiara Panicucci, Sara Pintus, Francesca Antonini, Genny Del Zotto, Andrea Benzi, Santina Bruzzone, Paolo Scudieri, Carlo Minetti, Elisabetta Gazzerro, Claudio Bruno
Summary: In this study, the therapeutic effectiveness of a selective P2X7 purinoreceptor antagonist, A438079, was evaluated in limb-girdle muscular dystrophy R3. The results showed that the P2X7 antagonist improved clinical parameters, reduced muscle inflammation and fibrosis, and upregulated immunosuppressive regulatory T cells.
Article
Biochemistry & Molecular Biology
Patrizia Spadafora, Antonio Qualtieri, Francesca Cavalcanti, Gemma Di Palma, Olivier Gallo, Selene De Benedittis, Annamaria Cerantonio, Luigi Citrigno
Summary: This study reports a new missense variant in the DYSF gene associated with LGMDR2/2B, identified through NGS technology. The variant was found in homozygosity in two sisters of the proband, indicating its probable pathological role in the onset of the disease. The study highlights the potential of NGS as a powerful tool for identifying LGMD subtypes and emphasizes the importance of collecting and sharing genetic data for further genetic-molecular research and personalized medicine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Shala Ghaderi Berntsson, Hans Matsson, Anna Kristoffersson, Valter Niemela, Hermine A. van Duyvenvoorde, Cindy Richel-van Assenbergh, Heleen M. van der Klift, Olivera Casar-Borota, Carina Frykholm, Anne-Marie Landtblom
Summary: In this study, we present the case of a male patient who developed muscle weakness in his teens, leading to walking difficulties in his twenties. Despite the initial investigation revealing no abnormalities in the dystrophin gene, immunohistochemistry and Western blot analysis suggested dystrophinopathy. After more than 10 years, RNA analysis identified abnormal splicing and a frameshift mutation in the DMD gene. Additionally, a novel variant was identified in the genomic DNA. This study demonstrates the importance of mRNA analysis in guiding the diagnosis of non-coding genetic variants in DMD.
FRONTIERS IN GENETICS
(2023)
Article
Clinical Neurology
Lais U. Aivazoglou, Julio B. Guimaraes, Maria Alice F. Costa, Andre Yui Aihara, Fabiano N. Cardoso, Wladimir B. V. De R. Pinto, Paulo Victor S. de Souza, Andre M. S. da Silva, Edmar Zanoteli, Acary S. B. Oliveira, Alzira A. S. Carvalho, Artur Da R. C. Fernandes
Summary: This study aimed to correlate MRI findings with functional scores and describe the WBMRI pattern in a Brazilian cohort of LGMDR1 patients. The results showed that the involvement of paraspinal muscles, including the lumbar erector spinae, was more severe in these patients, with a striped appearance present in approximately 72% of them. There was a positive correlation between MRI scores and functional scores. The study suggests that WBMRI can provide a comprehensive evaluation of LGMDR1 patients and may be useful for diagnostic and outcome measure selection in clinical trials.
Article
Genetics & Heredity
Sivan Lewis, Amy Woroch, Mary Kate Hatch, Reymundo Lozano
Summary: Limb-girdle muscular dystrophies are genetic disorders characterized by progressive proximal muscle weakness. This case report highlights the association between a specific variant in the SGCA gene and neurodevelopmental disorders in a 3-year-old boy with muscular weakness and elevated CK levels.
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)
Article
Biochemistry & Molecular Biology
Karima Relizani, Lucia Echevarria, Faouzi Zarrouki, Cecile Gastaldi, Chloe Dambrune, Philippine Aupy, Adrian Haeberli, Marek Komisarski, Thomas Tensorer, Thibaut Larcher, Fedor Svinartchouk, Cyrille Vaillend, Luis Garcia, Aurelie Goyenvalle
Summary: Tricyclo-DNA (tcDNA) is a promising oligonucleotide analog with therapeutic potential, especially when conjugated with palmitic acid for improved delivery to muscle tissues. This conjugation enhances the potency of tcDNA-ASO, resulting in functional improvement in dystrophic mice with significantly reduced dose, while also showing a promising safety profile for clinical development in neuromuscular diseases.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Clinical Neurology
Matthew Katz, Leigh B. Waddell, Michaela Yuen, Samantha J. Bryen, Emily Oates, Fleur C. Garton, Thomas Robertson, Robert David Henderson, Sandra T. Cooper, Pamela A. McCombe
Summary: This study reports two siblings with typical cerebral white matter changes and adult-onset limb girdle muscular dystrophy. They were found to have a previously unreported variant in the LAMA2 gene, expanding the genotypic and phenotypic spectrum of LGMDR23.
FRONTIERS IN NEUROLOGY
(2023)
Article
Oncology
Cheng Zhang, Xueping Zheng, Deguo Lu, Lulu Xu, Fengyuan Che, Shiguo Liu
Summary: A Chinese patient with limb-girdle muscular dystrophy recessive 1 was found to have compound heterozygous variants in the CAPN3 gene, expanding the variant spectrum of this gene. This discovery is important for improving the development of molecular diagnostic tools and providing genetic counseling for patients with a family history of the disease.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Medicine, General & Internal
Mark Richardson, Anna Mayhew, Robert Muni-Lofra, Lindsay B. Murphy, Volker Straub
Summary: The study aimed to determine the prevalence of pain in limb girdle muscular dystrophy R9 (LGMDR9) patients and its associations with genotypes, age, and ambulatory status. Findings showed that 87% of patients reported current pain, with 25% reporting severe current pain. The study concludes that pain should be considered a significant issue requiring management in individuals with LGMDR9.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Rheumatology
Italo Marago, Mark Roberts, Federico Roncaroli, Daniel DuPlessis, Caroline Sewry, Santhosh Nagaraju, Faheema Limbada, Chiara Marini-Bettolo, Judith Hudson, Siwalik Banerjee, Laura Newton, Marwan Bukhari, Hector Chinoy, James B. Lilleker
Summary: This study reviewed four patients initially misdiagnosed with IIM but later found to have LGMD 2 l, highlighting the importance of accurate diagnosis in differentiating non-inflammatory myopathies and avoiding inappropriate treatments. The patients had common features in clinical presentation, treatment response, and muscle imaging, emphasizing the need for clinicians to be aware of the potential mimicry of genetic myopathies in IIM diagnoses.
Article
Genetics & Heredity
Anna G. Shestak, Anna A. Bukaeva, Siamak Saber, Elena Zaklyazminskaya
Summary: Primary cardiomyopathies are monogenic disorders with multiple alleles influencing pathogenesis. Next-generation sequencing has improved DNA diagnostics but genetic testing for CMPs still has a diagnostic yield below 60%. The study identified allelic dropout as a common issue impacting diagnostic yield in genetic testing for primary cardiomyopathies.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Yulia Lutokhina, Olga Blagova, Alexander Panferov, Vsevolod Sedov, Evgeniya Kogan, Tatiana Nekrasova, Alexander Nedostup, Elena Zaklyazminskaya
Summary: Translation: A case study of a male patient with restrictive cardiomyopathy (RCM) and elevated serum iron levels and transferrin saturation percentage is reported. Mutations in desmin (DES) and hemochromatosis gene (HFE1) were identified. Liver biopsy confirmed drug-induced injury, subcompensated heart failure, and hemosiderin accumulation. Therefore, other less likely causes should be taken into consideration even if one obvious cause has been identified.
Article
Genetics & Heredity
Elena Zaklyazminskaya, Margarita Polyak, Anna Shestak, Mariam Sadekova, Vera Komoliatova, Irina Kiseleva, Leonid Makarov, Dmitriy Podolyak, Grigory Glukhov, Han Zhang, Denis Abramochkin, Olga S. Sokolova
Summary: This study identified three rare genetic variants in the KCNJ2 gene, one of which was reclassified as a variant of unknown significance. LQT7 is a rare form of LQTS in Russia.
Article
Cardiac & Cardiovascular Systems
O. Blagova, E. Pavlenko, N. V. Varionchik, V. P. Sedov, N. Gagarina, E. A. Mershina, M. E. Polyak, E. Zaklyazminskaya, A. Nedostup
Summary: The study aimed to investigate the position of NCM in the structure of DCM, its clinical features, and its influence on prognosis compared with other forms of DCM syndrome. The results showed that NCM is an independent form of DCM syndrome, characterized by a higher frequency of pathogenic mutations, arrhythmic events, worse response to cardiotropic therapy, and a higher frequency of intracardiac thrombosis.
RATIONAL PHARMACOTHERAPY IN CARDIOLOGY
(2022)
Article
Genetics & Heredity
Olga Blagova, Ekaterina Pavlenko, Vsevolod Sedov, Evgeniya Kogan, Margarita Polyak, Elena Zaklyazminskaya, Yulia Lutokhina
Summary: The same variants in sarcomeric genes can lead to different cardiomyopathies within the same family. This case report describes a familial sarcomeric cardiomyopathy caused by a specific pathogenic variant in the cardiac myosin-binding protein C gene, affecting multiple generations.
Article
Biochemistry & Molecular Biology
Andrey K. Tsaturyan, Elena V. Zaklyazminskaya, Margarita E. Polyak, Galina V. Kopylova, Daniil V. Shchepkin, Anastasia M. Kochurova, Anastasiia D. Gonchar, Sergey Y. Kleymenov, Natalia A. Koubasova, Sergey Y. Bershitsky, Alexander M. Matyushenko, Dmitrii I. Levitsky
Summary: The study identified a new variant in the TPM1 gene, which is associated with HCM. The variant increased the thermal stability of the Tpm molecule and its affinity for F-actin was unaffected. However, it increased the Ca2+ sensitivity of filament sliding and impaired its inhibition at low Ca2+ concentration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Y. A. Lutokhina, O. V. Blagova, P. O. Savina, E. V. Zaklyazminskaya
Summary: A 64-year-old female with a family history of hereditary hemorrhagic telangiectasia (HHT) presented with dyspnea and leg edema. Despite treatment, her heart failure worsened after each episode of massive blood loss. Echocardiography revealed high pulmonary hypertension. Interstitial lung lesions were detected on CT scan. The patient's condition improved with cardiotropic and diuretic therapy, but she ultimately died from acute progression of pulmonary hypertension. Timely diagnosis and treatment of pulmonary hypertension in HHT are crucial for prognosis.
RATIONAL PHARMACOTHERAPY IN CARDIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alexander M. Matyushenko, Victoria V. Nefedova, Anastasia M. Kochurova, Galina V. Kopylova, Natalia A. Koubassova, Anna G. Shestak, Daria S. Yampolskaya, Daniil V. Shchepkin, Sergey Y. Kleymenov, Natalia S. Ryabkova, Ivan A. Katrukha, Sergey Y. Bershitsky, Elena V. Zaklyazminskaya, Andrey K. Tsaturyan, Dmitrii I. Levitsky
Summary: We characterized a novel genetic variant c.292G > A (p.E98K) in the TPM1 gene encoding cardiac tropomyosin 1.1 isoform (Tpm1.1), which is associated with complex cardiomyopathy, conduction dysfunction, and neuromuscular involvement. We found that the E98K substitution in Tpm1.1 significantly destabilizes its structure and impairs its regulatory properties. This study provides insights into the mechanism by which the E98K Tpm mutation affects myocardial function and relaxation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Cardiac & Cardiovascular Systems
Y. A. Lutokhina, O. V. Blagova, A. G. Shestak, M. E. Polyak, A. A. Bukaeva, E. V. Zaklyazminskaya, N. V. Varionchik, V. P. Sedov, E. A. Kogan, S. A. Alexandrova, A. V. Nedostup
EUROPEAN HEART JOURNAL
(2021)
Review
Crystallography
Y. G. Kacher, M. G. Karlova, G. S. Glukhov, H. Zhang, E. V. Zaklyazminskaya, G. Loussouarn, O. S. Sokolova
Summary: Membrane proteins, especially ion channels, became the focus of structural proteomics in the mid-20th century. Studies on ion channels involve diverse methods, including structural (such as X-ray crystallography, cryoelectron microscopy, and patch clamp) and functional approaches. The contribution of electrophysiological studies and molecular dynamics, along with advancements in X-ray crystallography and cryoelectron microscopy, have enabled the obtainment of atomic structure of ion channels.
CRYSTALLOGRAPHY REPORTS
(2021)
Meeting Abstract
Biochemistry & Molecular Biology
Y. Kacher, M. Karlova, V. Rusinova, D. Abramochkin, E. Zaklyazminskaya, O. S. Sokolova
Meeting Abstract
Biophysics
Julia Kacher, Maria Karlova, Valeria Rusinova, Denis Abramochkin, Elena Zaklyazminskaya, Olga Sokolova
BIOPHYSICAL JOURNAL
(2021)
Article
Cardiac & Cardiovascular Systems
Yulia Lutokhina, Olga Blagova, Nadezhda Varionchik, Svetlana Alexandrova, Nina Gagarina, Eugenia Kogan, Vsevolod Sedov, Anna Shestak, Elena Zaklyazminskaya, Alexander Nedostup
Summary: In a young patient with arrhythmogenic syncope and dilated cardiomyopathy (DCM), a diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) and left ventricular noncompaction (LVNC) with biopsy-proven virus-negative chronic myocarditis was made. The use of immunosuppressive therapy stabilized heart function and decreased the risk of arrhythmic events. The combination of myocarditis and primary cardiomyopathy is not rare in DCM syndrome.
Article
Genetics & Heredity
Xiangge Meng, Chengping Li, Yu Hei, Xiang Zhou, Guoli Zhou
Summary: The study used IVT-SAPAS sequencing to analyze the dynamic changes of APA sites during adipogenesis in bovine subcutaneous preadipocytes and intramuscular preadipocytes. The results showed that APA plays an important role in adipocyte differentiation, and UTR-APA switching genes have different trends, with intramuscular preadipocytes tending to use shorter 3'UTR for differentiation. TRIB3, WWTR1, and INSIG1 play important roles in intramuscular preadipocyte differentiation.
Article
Genetics & Heredity
S. Alizadeh, S. Khamse, N. Tajeddin, H. R. Khorram Khorshid, A. Delbari, M. Ohadi
Summary: This study identifies a specific genotype at a CG-rich trinucleotide short tandem repeat (STR) locus that is associated with late-onset neurocognitive disorders such as Alzheimer's disease (AD).
Article
Genetics & Heredity
Shougang Liu, Zhe Zhuang, Fanghua Liu, Xiuqing Yuan, Zeqiao Zhang, Xiaoqian Liang, Xinhui Li, Yongfeng Chen
Summary: This study investigated the effect and mechanism of RPL9 and TIFA in scalp psoriasis, and identified RPL9 as a potential therapeutic target for scalp psoriasis.
Article
Genetics & Heredity
Shiting Wang, Jiaqi Chen, Zhichao Jin, Ying Xing, Ruiping Wang
Summary: This study suggests a causal association between hair color and skin cancers, with light hair colors (red, blonde, and light brown) being associated with an increased risk and dark brown hair being associated with a decreased risk.
Article
Genetics & Heredity
Joseph Hawadak, Loick Pradel Kojom Foko, Rodrigue Roman Dongang Nana, Karmveer Yadav, Veena Pande, Aparup Das, Vineeta Singh
Summary: This study investigates the genetic diversity and natural selection of the Pfama-1 gene in Plasmodium falciparum isolates from Cameroon. The study finds a considerable nucleotide and haplotype diversity, as well as specific mutations in Cameroonian isolates. Positive diversifying selection and the identification of selected codon sites suggest the potential implication of these genetic variations in host immune pressure and parasite-binding complex modulation. The findings provide valuable baseline data for malaria vaccine design.
Article
Genetics & Heredity
Emily Biernat, Mansi Verma, Chhabi K. Govind
Summary: RSC is an essential ATP-dependent chromatin remodeling complex in Saccharomyces cerevisiae. It regulates nucleosome-depleted regions (NDRs) by sliding flanking nucleosomes away from NDRs. Depletion of RSC leads to nucleosome encroachment in NDRs and transcription initiation defects. The study compared the effects of catalytic-dead Sth1 and rapid depletion of Sth1 on transcription. Rapid depletion of Sth1 reduces recruitment of TBP and Pol II, while the catalytic-dead mutant exhibits a severe reduction in TBP binding but accumulates Pol II in coding regions. The results suggest a role for RSC in transcription elongation and termination processes.
Article
Genetics & Heredity
Yunxiao Wei, Yuhan Song, Muhammad Aamir Khan, Chengzhen Liang, Zhigang Meng, Yuan Wang, Sandui Guo, Rui Zhang
Summary: This study analyzed the GhTPP protein family in upland cotton for the first time and identified the important role of GhTPPA_2 in regulating sugar metabolism, improving soluble sugar accumulation, and drought stress tolerance.
Article
Genetics & Heredity
Yannan Geng, Rui Shao, Tiantong Xu, Lilong Zhang
Summary: A novel risk model based on SCUBE3, TNNC1, SPON1, SEPT12 and ULBP1 genes was developed for predicting PMOP risk, with higher risk score indicating higher risk of suffering from PMOP. Significant differences in signaling pathway activities were observed between the high-risk score group and the low-risk score group.
Article
Genetics & Heredity
Randy P. Williams, Corina Lesseur, Haoxiang Cheng, Qian Li, Maya Deyssenroth, Christopher D. Molteno, Ernesta M. Meintjes, Sandra W. Jacobson, Joseph L. Jacobson, Helen Wainwright, Ke Hao, Jia Chen, R. Colin Carter
Summary: The study suggests that heavy alcohol exposure during pregnancy may impact the proportion of fetal placental villi macrophages and increase the expression of inflammatory genes. Further research is needed to explore these effects and evaluate the potential functional roles of placental inflammation in FASD.
Article
Genetics & Heredity
Lvjing Luo, Lishuang Sun, Shu Li, Huiting Liu, Zhengyu Chen, Shi Huang, Yinyin Mo, Genliang Li
Summary: This study analyzed the expression of Ptpn1 and miR-124-3p in testicular tissues of mice and investigated their regulatory relationship. The results showed that Ptpn1 expression was up-regulated in adult mouse testis compared to juvenile mouse testis, while miR-124-3p expression showed an opposite pattern. Further analysis suggested that the down-regulation of miR-124-3p may contribute to the high expression of Ptpn1 in adult mouse testis.
Article
Genetics & Heredity
Gairui Li, Dan Zhao, Xiaolin Peng, Yashuang Zhao
Summary: MiRNA-22 shows potential as a candidate for early diagnosis of colorectal cancer (CRC). The study found higher miR-22 expression levels in the CRC and CRA groups, suggesting its potential as a biomarker for CRC early screening.
Article
Genetics & Heredity
Zhongqiu Zhu, Qianting Yang, Xiaoying Tian, Da Man, Jian Wang, Junfang Zhang, Bingshe Han
Summary: This study constructed a ceRNA network mediated by lncRNAs in cold-acclimated zebrafish ZF4 cells and revealed that upregulation of MSTRG3207 promotes apoptosis by sponging dre-miR-736 during cold acclimation.
Article
Genetics & Heredity
Weitao Chen, Denggao Xiang, Shang Gao, Shuli Zhu, Zhi Wu, Yuefei Li, Jie Li
Summary: Dam construction has negatively impacted the genetic diversity and structure of fish populations. This case study on the endangered Hemibagrus guttatus found low genetic diversity, high levels of inbreeding, and decreasing population size in fragmented populations. Genetic structure and differentiation were also observed, indicating the influence of dams on these fish populations.
Article
Genetics & Heredity
Pooja Singh, Debleena Guin, Bijay Pattnaik, Ritushree Kukreti
Summary: Through systematic literature review and meta-analysis, it was found that idiopathic pulmonary fibrosis is significantly associated with 222 polymorphisms in 118 genes. Four polymorphisms - rs35705950/MUC5B, rs2736100/TERT, rs2076295/DSP, and rs111521887/TOLLIP, exhibited substantial epidemiological evidence supporting their association with IPF risk.
Article
Genetics & Heredity
Jianping Zhang, Zhijun Cai, Fanzhe Feng, Yufeng Peng, Yi Cui, Yongiqing Xu
Summary: This study found that exosomes secreted by young BMSCs can promote the healing of tendon-bone interface after rotator cuff tears. These exosomes can improve extracellular matrix remodeling, osteogenic differentiation, angiogenesis, and stemness of tendon-derived stem cells (TDSCs). The exosomes from young BMSCs have better effects compared to those from aged BMSCs.