8 results on '"Bratkovic, Drago"'
Search Results
2. Additional file 1: of A study on the safety and efficacy of reveglucosidase alfa in patients with late-onset Pompe disease
- Author
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Byrne, Barry, Tarekegn Geberhiwot, Barshop, Bruce, Barohn, Richard, Derralynn Hughes, Bratkovic, Drago, Desnuelle, Claude, Laforet, Pascal, Mengel, Eugen, Roberts, Mark, Haroldsen, Peter, Reilley, Kristin, Jayaram, Kala, Yang, Ke, and Walsh, Liron
- Abstract
GAA activity and genotype by subject. (DOCX 13Â kb)
- Published
- 2017
- Full Text
- View/download PDF
3. Additional file 3: of A study on the safety and efficacy of reveglucosidase alfa in patients with late-onset Pompe disease
- Author
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Byrne, Barry, Tarekegn Geberhiwot, Barshop, Bruce, Barohn, Richard, Derralynn Hughes, Bratkovic, Drago, Desnuelle, Claude, Laforet, Pascal, Mengel, Eugen, Roberts, Mark, Haroldsen, Peter, Reilley, Kristin, Jayaram, Kala, Yang, Ke, and Walsh, Liron
- Abstract
Change from baseline in maximum voluntary ventilation (MVV). Mean changes from baseline to week 72 in subjects receiving 20Â mg/kg reveglucosidase alfa infusion every 2Â weeks. Baseline is defined as the last measurement prior to the first infusion. The error bars represent the standard deviations. The statistical significance of treatment effects was not determined, as no pre-planned statistical analyses were conducted for this study. (PDF 122Â kb)
- Published
- 2017
- Full Text
- View/download PDF
4. Additional file 2: of A study on the safety and efficacy of reveglucosidase alfa in patients with late-onset Pompe disease
- Author
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Byrne, Barry, Tarekegn Geberhiwot, Barshop, Bruce, Barohn, Richard, Derralynn Hughes, Bratkovic, Drago, Desnuelle, Claude, Laforet, Pascal, Mengel, Eugen, Roberts, Mark, Haroldsen, Peter, Reilley, Kristin, Jayaram, Kala, Yang, Ke, and Walsh, Liron
- Subjects
stomatognathic system ,fungi ,virus diseases ,digestive system diseases - Abstract
Mean anti-BMN 701 (reveglucosidase alfa) antibody titers (safety population). (DOCX 16Â kb)
- Published
- 2017
- Full Text
- View/download PDF
5. Pathogenic variants in glutamyl-tRNAGln amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder
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Friederich, Marisa W, Timal, Sharita, Powell, Christopher A, Dallabona, Cristina, Kurolap, Alina, Palacios-Zambrano, Sara, Bratkovic, Drago, Derks, Terry GJ, Bick, David, Bouman, Katelijne, Chatfield, Kathryn C, Damouny-Naoum, Nadine, Dishop, Megan K, Falik-Zaccai, Tzipora C, Fares, Fuad, Fedida, Ayalla, Ferrero, Ileana, Gallagher, Renata C, Garesse, Rafael, Gilberti, Micol, González, Cristina, Gowan, Katherine, Habib, Clair, Halligan, Rebecca K, Kalfon, Limor, Knight, Kaz, Lefeber, Dirk, Mamblona, Laura, Mandel, Hanna, Mory, Adi, Ottoson, John, Paperna, Tamar, Pruijn, Ger JM, Rebelo-Guiomar, Pedro F, Saada, Ann, Sainz, Bruno, Salvemini, Hayley, Schoots, Mirthe H, Smeitink, Jan A, Szukszto, Maciej J, Ter Horst, Hendrik J, Van Den Brandt, Frans, Van Spronsen, Francjan J, Veltman, Joris A, Wartchow, Eric, Wintjes, Liesbeth T, Zohar, Yaniv, Fernández-Moreno, Miguel A, Baris, Hagit N, Donnini, Claudia, Minczuk, Michal, Rodenburg, Richard J, and Van Hove, Johan LK
- Subjects
Male ,Models, Molecular ,Mitochondrial Diseases ,Myocardium ,Nitrogenous Group Transferases ,Lentivirus ,Infant, Newborn ,Infant ,Saccharomyces cerevisiae ,Fibroblasts ,Oxidative Phosphorylation ,3. Good health ,Pedigree ,Protein Subunits ,RNA, Transfer ,Protein Biosynthesis ,Mutation ,Humans ,Female ,Amino Acid Sequence ,Cardiomyopathies - Abstract
Mitochondrial protein synthesis requires charging mt-tRNAs with their cognate amino acids by mitochondrial aminoacyl-tRNA synthetases, with the exception of glutaminyl mt-tRNA (mt-tRNAGln). mt-tRNAGln is indirectly charged by a transamidation reaction involving the GatCAB aminoacyl-tRNA amidotransferase complex. Defects involving the mitochondrial protein synthesis machinery cause a broad spectrum of disorders, with often fatal outcome. Here, we describe nine patients from five families with genetic defects in a GatCAB complex subunit, including QRSL1, GATB, and GATC, each showing a lethal metabolic cardiomyopathy syndrome. Functional studies reveal combined respiratory chain enzyme deficiencies and mitochondrial dysfunction. Aminoacylation of mt-tRNAGln and mitochondrial protein translation are deficient in patients' fibroblasts cultured in the absence of glutamine but restore in high glutamine. Lentiviral rescue experiments and modeling in S. cerevisiae homologs confirm pathogenicity. Our study completes a decade of investigations on mitochondrial aminoacylation disorders, starting with DARS2 and ending with the GatCAB complex.
6. Mutations in ELAC2 associated with hypertrophic cardiomyopathy impair mitochondrial tRNA 3'-end processing
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Saoura, Makenzie, Powell, Christopher A, Kopajtich, Robert, Alahmad, Ahmad, Al-Balool, Haya H, Albash, Buthaina, Alfadhel, Majid, Alston, Charlotte L, Bertini, Enrico, Bonnen, Penelope E, Bratkovic, Drago, Carrozzo, Rosalba, Donati, Maria A, Di Nottia, Michela, Ghezzi, Daniele, Goldstein, Amy, Haan, Eric, Horvath, Rita, Hughes, Joanne, Invernizzi, Federica, Lamantea, Eleonora, Lucas, Benjamin, Pinnock, Kyla-Gaye, Pujantell, Maria, Rahman, Shamima, Rebelo-Guiomar, Pedro, Santra, Saikat, Verrigni, Daniela, McFarland, Robert, Prokisch, Holger, Taylor, Robert W, Levinger, Louis, and Minczuk, Michal
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Male ,Genotype ,Protein Conformation ,Gene Expression ,Substrate Specificity ,Cohort Studies ,Structure-Activity Relationship ,RNA, Transfer ,Humans ,Genetic Predisposition to Disease ,Protein Interaction Domains and Motifs ,RNA Processing, Post-Transcriptional ,Alleles ,Genetic Association Studies ,Infant ,Cardiomyopathy, Hypertrophic ,3. Good health ,Mitochondria ,Neoplasm Proteins ,Enzyme Activation ,mitochondrial disease ,Kinetics ,Genes, Mitochondrial ,Phenotype ,Amino Acid Substitution ,Mutation ,RNA ,Female ,cardiomyopathy ,Biomarkers ,RNase Z - Abstract
Mutations in either the mitochondrial or nuclear genomes are associated with a diverse group of human disorders characterized by impaired mitochondrial respiration. Within this group, an increasing number of mutations have been identified in nuclear genes involved in mitochondrial RNA metabolism, including ELAC2. The ELAC2 gene codes for the mitochondrial RNase Z, responsible for endonucleolytic cleavage of the 3' ends of mitochondrial pre-tRNAs. Here, we report the identification of 16 novel ELAC2 variants in individuals presenting with mitochondrial respiratory chain deficiency, hypertrophic cardiomyopathy (HCM), and lactic acidosis. We provide evidence for the pathogenicity of the novel missense variants by studying the RNase Z activity in an in vitro system. We also modeled the residues affected by a missense mutation in solved RNase Z structures, providing insight into enzyme structure and function. Finally, we show that primary fibroblasts from the affected individuals have elevated levels of unprocessed mitochondrial RNA precursors. Our study thus broadly confirms the correlation of ELAC2 variants with severe infantile-onset forms of HCM and mitochondrial respiratory chain dysfunction. One rare missense variant associated with the occurrence of prostate cancer (p.Arg781His) impairs the mitochondrial RNase Z activity of ELAC2, suggesting a functional link between tumorigenesis and mitochondrial RNA metabolism.
7. Identification and targeted management of a neurodegenerative disorder caused by biallelic mutations in SLC5A6
- Author
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Alicia B. Byrne, Peer Arts, Christopher N. Hahn, Steven W. Polyak, Dylan A. Mordaunt, Nicholas J.C. Smith, Hamish S. Scott, Andreas W. Schreiber, Janice M. Fletcher, Drago Bratkovic, Grant W. Booker, Jillian Lipsett, Karin S. Kassahn, Jinghua Feng, Byrne, Alicia B, Arts, Peer, Polyak, Steven W, Feng, Jinghua, Schreiber, Andreas, Kassahn, Karin S, Hahn, Christopher N, Mordaunt, Dylan A, Fletcher, Janice M, Lipsett, Jillian, Bratkovic, Drago, Booker, Grant W, Smith, Nicholas J, and Scott, Hamish S
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0301 basic medicine ,Vitamin ,lcsh:QH426-470 ,Mutant ,Metabolic disorders ,lcsh:Medicine ,Case Report ,Compound heterozygosity ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Biotin ,Genetics ,medicine ,Molecular Biology ,Genetics (clinical) ,Exome sequencing ,SLC5A6 mutations ,business.industry ,lcsh:R ,Neurodevelopmental disorders ,Genetic disorder ,Transporter ,Translational research ,medicine.disease ,Personalized medicine ,Phenotype ,3. Good health ,lcsh:Genetics ,030104 developmental biology ,chemistry ,business ,neurodegenerative disorder ,Medical genomics ,030217 neurology & neurosurgery ,biallelic mutations - Abstract
We describe a sibling pair displaying an early infantile-onset, progressive neurodegenerative phenotype, with symptoms of developmental delay and epileptic encephalopathy developing from 12 to 14 months of age. Using whole exome sequencing, compound heterozygous variants were identified in SLC5A6, which encodes the sodium-dependent multivitamin transporter (SMVT) protein. SMVT is an important transporter of the B-group vitamins biotin, pantothenate, and lipoate. The protein is ubiquitously expressed and has major roles in vitamin uptake in the digestive system, as well as transport of these vitamins across the blood–brain barrier. Pathogenicity of the identified variants was demonstrated by impaired biotin uptake of mutant SMVT. Identification of this vitamin transporter as the genetic basis of this disorder guided targeted therapeutic intervention, resulting clinically in improvement of the patient’s neurocognitive and neuromotor function. This is the second report of biallelic mutations in SLC5A6 leading to a neurodegenerative disorder due to impaired biotin, pantothenate and lipoate uptake. The genetic and phenotypic overlap of these cases confirms mutations in SLC5A6 as the genetic cause of this disease phenotype. Recognition of the genetic disorder caused by SLC5A6 mutations is essential for early diagnosis and to facilitate timely intervention by triple vitamin (biotin, pantothenate, and lipoate) replacement therapy.
- Published
- 2019
8. Presentation of m.3243AG (MT-TL1; tRNALeu) variant with focal neurology in infancy
- Author
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David Ketteridge, Dylan A. Mordaunt, Hamish S. Scott, Drago Bratkovic, Karin S. Kassahn, Afdal Ibrahim, Nicholas Smith, Liam C. McIntyre, Hayley Salvemini, Mordaunt, David A, McIntyre, Liam C, Salvemini, Hayley, Ibrahim, Afdal, Bratkovic, Drago, Ketteridge, David, Scott, Hamish S, Kassahn, Karin S, and Smith, Nicholas
- Subjects
Male ,Hemiparesis ,G%22">M.3243A>G ,medicine.medical_specialty ,Mitochondrial DNA ,Neurology ,RNA, Transfer, Leu ,Encephalopathy ,Mitochondrion ,Biology ,medicine.disease_cause ,DNA, Mitochondrial ,7q36.3 duplication ,Genetics ,medicine ,Humans ,Exome ,Genetics (clinical) ,Mutation ,Infant, Newborn ,Infant ,Sequence Analysis, DNA ,medicine.disease ,Magnetic Resonance Imaging ,Mitochondria ,Maternally inherited diabetes and deafness (MIDD) ,MT-TL1 ,Lactic acidosis ,Child, Preschool ,Female ,Nervous System Diseases - Abstract
The Mitochondrial tRNALeu (MT-TL1) mutation, m.3243A>G constitutes the commonest identified mitochondrial genome mutation. Characteristically, giving rise to MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes), a phenotypic spectrum associated with this genetic variant is now apparent. We report on the first patient with infantile hemiparesis, without comorbid encephalopathy, attributed to this variant. This further expands the recognized disease spectrum and highlights the need to consider mitochondrial genomic mutations in cases of cryptogenic focal neurological deficit in infancy. The potential for genetic disease modifiers is additionally discussed. usc Refereed/Peer-reviewed
- Published
- 2014
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