A novel pathogenic variant in TNPO3 in a Hungarian family with limb-girdle muscular dystrophy 1F |
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| Affiliation: | 1. Department of Medicine, University of Vermont, Burlington, Vermont, USA. ISCT Chief Scientific Officer 2014–2016. Chair, ISCT Pulmonary Committee 2013–2015;2. Department of Cell & Molecular Therapies, Royal Prince Alfred Hospital, Centenary Institute, Sydney Medical School, University of Sydney, Sydney, Australia. ISCT Australia & New Zealand, Past Regional Vice President 2008–2012;3. Andalusian Initiative for Advanced Therapies, Junta de Andalucía, Sevilla, Spain. Chair, ISCT EU LRA Committee, 2014–2016;4. Bone Marrow Transplantation and Cell Therapy Unit, Associação Portuguesa de Beneficencia, SJ Rio Preto, Sao Paulo, Brazil. ISCT South & Central America, Past Regional Vice President 2013–2015;5. Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan. ISCT Asia, Past Regional Vice President 2013–2015;6. Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia. ISCT Australia & New Zealand, Regional Vice-President 2014–2016;7. Western Australian Neuroscience Research Institute, Centre for Comparative Genomics, Murdoch University, Perth, Australia. Member at large of the ISCT Presidential Task Force on the Use of Unproven Cellular Therapies;8. Division of Oncology, Laboratory of Cellular Therapy, University of Modena & Reggio Emilia, Modena, Italy. ISCT President 2014–2016. Chair of the ISCT Presidential Task Force on the Use of Unproven Cellular Therapies;9. Center for Stem Cell Research (a unit of inStem, Bengaluru), Department of Hematology, Christian Medical College, Vellore, India. Member at large of the ISCT Presidential Task Force on the Use of Unproven Cellular Therapies |
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| Abstract: | Limb-girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous muscular diseases that predominantly affect the proximal muscles. Pathogenic variants in TNPO3 have been associated with a rare, autosomal dominant limb-girdle muscular dystrophy 1F (LGMD1F) in a large Italian-Spanish family and an isolated LGMD1F case. Here we present two individuals from a Hungarian family with an early-onset, slowly progressive muscular dystrophy. Both the female proband and her affected son had delayed early motor milestones including first walking at 14 months and 18 months, respectively. Both present with progressive weakness of facial, bulbar, axial, and distal muscles especially of the lower extremities. Electromyography indicated myogenic damage and muscle biopsy from the proband showed myopathic alterations with sarcoplasmic masses and signs of mitochondrial dysfunction. Exome sequencing of the female proband identified a novel c.2767delC p.(Arg923AspfsTer17) variant in TNPO3. Sanger sequencing confirmed the presence of the TNPO3 variant in the affected son; the unaffected son did not have the variant. The identification of the c.2767delC variant further supports the clinical significance of TNPO3 and expands the clinical spectrum of TNPO3-associated LGMD1F. |
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| Keywords: | Limb-girdle muscular dystrophy (LGMD) Transportin 3 (TNPO3) Exome sequencing |
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