title: Tubular Aggregates and Cylindrical Spirals Have Distinct Immunohistochemical Signatures.
abstract: Tubular aggregates and cylindrical spirals are 2 distinct ultrastructural abnormalities observed in muscle biopsies that have similar histochemical staining characteristics on light microscopy. Both are found in a wide range of disorders. Recently, a number of genetic mutations have been reported in conditions with tubular aggregates in skeletal muscle. It is widely accepted that tubular aggregates arise from the sarcoplasmic reticulum, but the origin of cylindrical spirals has been less clearly defined. We describe the histopathological features of myopathies with tubular aggregates, including a detailed immunohistochemical analysis of congenital myasthenic syndromes with tubular aggregates due to mutations in GFPT1 and DPAGT1, and myopathies with cylindrical spirals. Our findings support the notion that cylindrical spirals, like tubular aggregates, derive primarily from the sarcoplasmic reticulum; however, immunohistochemistry indicates that different molecular components of the sarcoplasmic reticulum may be involved and can be used to distinguish between these different inclusions. The immunohistochemical differences may also help to guide genetic testing.
authors.affiliation: From the Department of Neurology, Southmead Hospital, Bristol, UK (SB); Department of Neuropathology, Royal Victoria Hospital, N. Ireland, Belfast, Northern Ireland (EGH); UCL Institute of Neurology, Queen Square, London, UK (QG, HH, JLH); MRC Centre for Neuromuscular Diseases, University College Hospitals, London, UK (MP, RQ, MGH); Department of Neurology, Queen Elizabeth Hospital, Birmingham, UK (SJ); Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, UK (EC); King's College London, MRC London Neurodegenerative Diseases Brain Bank, London, UK (SA-S); Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK (CAS); and Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK (DB).
authors.forename: Stefen
authors.initials: S
authors.lastname: Brady
authors.affiliation: From the Department of Neurology, Southmead Hospital, Bristol, UK (SB); Department of Neuropathology, Royal Victoria Hospital, N. Ireland, Belfast, Northern Ireland (EGH); UCL Institute of Neurology, Queen Square, London, UK (QG, HH, JLH); MRC Centre for Neuromuscular Diseases, University College Hospitals, London, UK (MP, RQ, MGH); Department of Neurology, Queen Elizabeth Hospital, Birmingham, UK (SJ); Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, UK (EC); King's College London, MRC London Neurodegenerative Diseases Brain Bank, London, UK (SA-S); Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK (CAS); and Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK (DB).
authors.forename: Estelle G
authors.initials: EG
authors.lastname: Healy
authors.affiliation: From the Department of Neurology, Southmead Hospital, Bristol, UK (SB); Department of Neuropathology, Royal Victoria Hospital, N. Ireland, Belfast, Northern Ireland (EGH); UCL Institute of Neurology, Queen Square, London, UK (QG, HH, JLH); MRC Centre for Neuromuscular Diseases, University College Hospitals, London, UK (MP, RQ, MGH); Department of Neurology, Queen Elizabeth Hospital, Birmingham, UK (SJ); Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, UK (EC); King's College London, MRC London Neurodegenerative Diseases Brain Bank, London, UK (SA-S); Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK (CAS); and Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK (DB).
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gang
authors.affiliation: From the Department of Neurology, Southmead Hospital, Bristol, UK (SB); Department of Neuropathology, Royal Victoria Hospital, N. Ireland, Belfast, Northern Ireland (EGH); UCL Institute of Neurology, Queen Square, London, UK (QG, HH, JLH); MRC Centre for Neuromuscular Diseases, University College Hospitals, London, UK (MP, RQ, MGH); Department of Neurology, Queen Elizabeth Hospital, Birmingham, UK (SJ); Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, UK (EC); King's College London, MRC London Neurodegenerative Diseases Brain Bank, London, UK (SA-S); Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK (CAS); and Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK (DB).
authors.forename: Matt
authors.initials: M
authors.lastname: Parton
authors.affiliation: From the Department of Neurology, Southmead Hospital, Bristol, UK (SB); Department of Neuropathology, Royal Victoria Hospital, N. Ireland, Belfast, Northern Ireland (EGH); UCL Institute of Neurology, Queen Square, London, UK (QG, HH, JLH); MRC Centre for Neuromuscular Diseases, University College Hospitals, London, UK (MP, RQ, MGH); Department of Neurology, Queen Elizabeth Hospital, Birmingham, UK (SJ); Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, UK (EC); King's College London, MRC London Neurodegenerative Diseases Brain Bank, London, UK (SA-S); Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK (CAS); and Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK (DB).
authors.forename: Ros
authors.initials: R
authors.lastname: Quinlivan
authors.affiliation: From the Department of Neurology, Southmead Hospital, Bristol, UK (SB); Department of Neuropathology, Royal Victoria Hospital, N. Ireland, Belfast, Northern Ireland (EGH); UCL Institute of Neurology, Queen Square, London, UK (QG, HH, JLH); MRC Centre for Neuromuscular Diseases, University College Hospitals, London, UK (MP, RQ, MGH); Department of Neurology, Queen Elizabeth Hospital, Birmingham, UK (SJ); Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, UK (EC); King's College London, MRC London Neurodegenerative Diseases Brain Bank, London, UK (SA-S); Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK (CAS); and Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK (DB).
authors.forename: Saiju
authors.initials: S
authors.lastname: Jacob
authors.affiliation: From the Department of Neurology, Southmead Hospital, Bristol, UK (SB); Department of Neuropathology, Royal Victoria Hospital, N. Ireland, Belfast, Northern Ireland (EGH); UCL Institute of Neurology, Queen Square, London, UK (QG, HH, JLH); MRC Centre for Neuromuscular Diseases, University College Hospitals, London, UK (MP, RQ, MGH); Department of Neurology, Queen Elizabeth Hospital, Birmingham, UK (SJ); Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, UK (EC); King's College London, MRC London Neurodegenerative Diseases Brain Bank, London, UK (SA-S); Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK (CAS); and Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK (DB).
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Curtis
authors.affiliation: From the Department of Neurology, Southmead Hospital, Bristol, UK (SB); Department of Neuropathology, Royal Victoria Hospital, N. Ireland, Belfast, Northern Ireland (EGH); UCL Institute of Neurology, Queen Square, London, UK (QG, HH, JLH); MRC Centre for Neuromuscular Diseases, University College Hospitals, London, UK (MP, RQ, MGH); Department of Neurology, Queen Elizabeth Hospital, Birmingham, UK (SJ); Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, UK (EC); King's College London, MRC London Neurodegenerative Diseases Brain Bank, London, UK (SA-S); Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK (CAS); and Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK (DB).
authors.forename: Safa
authors.initials: S
authors.lastname: Al-Sarraj
authors.affiliation: From the Department of Neurology, Southmead Hospital, Bristol, UK (SB); Department of Neuropathology, Royal Victoria Hospital, N. Ireland, Belfast, Northern Ireland (EGH); UCL Institute of Neurology, Queen Square, London, UK (QG, HH, JLH); MRC Centre for Neuromuscular Diseases, University College Hospitals, London, UK (MP, RQ, MGH); Department of Neurology, Queen Elizabeth Hospital, Birmingham, UK (SJ); Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, UK (EC); King's College London, MRC London Neurodegenerative Diseases Brain Bank, London, UK (SA-S); Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK (CAS); and Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK (DB).
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sewry
authors.affiliation: From the Department of Neurology, Southmead Hospital, Bristol, UK (SB); Department of Neuropathology, Royal Victoria Hospital, N. Ireland, Belfast, Northern Ireland (EGH); UCL Institute of Neurology, Queen Square, London, UK (QG, HH, JLH); MRC Centre for Neuromuscular Diseases, University College Hospitals, London, UK (MP, RQ, MGH); Department of Neurology, Queen Elizabeth Hospital, Birmingham, UK (SJ); Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, UK (EC); King's College London, MRC London Neurodegenerative Diseases Brain Bank, London, UK (SA-S); Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK (CAS); and Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK (DB).
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hanna
authors.affiliation: From the Department of Neurology, Southmead Hospital, Bristol, UK (SB); Department of Neuropathology, Royal Victoria Hospital, N. Ireland, Belfast, Northern Ireland (EGH); UCL Institute of Neurology, Queen Square, London, UK (QG, HH, JLH); MRC Centre for Neuromuscular Diseases, University College Hospitals, London, UK (MP, RQ, MGH); Department of Neurology, Queen Elizabeth Hospital, Birmingham, UK (SJ); Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, UK (EC); King's College London, MRC London Neurodegenerative Diseases Brain Bank, London, UK (SA-S); Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK (CAS); and Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK (DB).
authors.forename: Henry
authors.initials: H
authors.lastname: Houlden
authors.affiliation: From the Department of Neurology, Southmead Hospital, Bristol, UK (SB); Department of Neuropathology, Royal Victoria Hospital, N. Ireland, Belfast, Northern Ireland (EGH); UCL Institute of Neurology, Queen Square, London, UK (QG, HH, JLH); MRC Centre for Neuromuscular Diseases, University College Hospitals, London, UK (MP, RQ, MGH); Department of Neurology, Queen Elizabeth Hospital, Birmingham, UK (SJ); Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, UK (EC); King's College London, MRC London Neurodegenerative Diseases Brain Bank, London, UK (SA-S); Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK (CAS); and Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK (DB).
authors.forename: David
authors.initials: D
authors.lastname: Beeson
authors.affiliation: From the Department of Neurology, Southmead Hospital, Bristol, UK (SB); Department of Neuropathology, Royal Victoria Hospital, N. Ireland, Belfast, Northern Ireland (EGH); UCL Institute of Neurology, Queen Square, London, UK (QG, HH, JLH); MRC Centre for Neuromuscular Diseases, University College Hospitals, London, UK (MP, RQ, MGH); Department of Neurology, Queen Elizabeth Hospital, Birmingham, UK (SJ); Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, UK (EC); King's College London, MRC London Neurodegenerative Diseases Brain Bank, London, UK (SA-S); Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK (CAS); and Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK (DB) janice.holton@ucl.ac.uk.
authors.forename: Janice L
authors.initials: JL
authors.lastname: Holton
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000473:pathology*; D018482:Muscle, Skeletal / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics / Q000473:pathology; D020914:Myopathies, Structural, Congenital / Q000235:genetics* / Q000473:pathology*; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics; D055815:Young Adult
chemical_list: D017351:N-Acetylglucosaminyltransferases; C047835:dolichyl-phosphate alpha-N-acetylglucosaminyltransferase; C497511:GFPT1 protein, human; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
keywords: Congenital myasthenic syndromes; Cylindrical spirals; Tubular aggregate myopathy.; Tubular aggregates