Case report: A novel ACTA1 variant in a patient with nemaline rods and increased glycogen deposition
BackgroundCongenital myopathies are a group of heterogeneous inherited disorders, mainly characterized by early-onset hypotonia and muscle weakness. The spectrum of clinical phenotype can be highly variable, going from very mild to severe presentations. The course also varies broadly resulting in a...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-03-01
|
| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2024.1340693/full |
| _version_ | 1797279268180328448 |
|---|---|
| author | Daniela Piga Martina Rimoldi Martina Rimoldi Francesca Magri Simona Zanotti Laura Napoli Michela Ripolone Serena Pagliarani Patrizia Ciscato Daniele Velardo Adele D’Amico Enrico Bertini Giacomo Pietro Comi Giacomo Pietro Comi Dario Ronchi Dario Ronchi Stefania Corti Stefania Corti |
| author_facet | Daniela Piga Martina Rimoldi Martina Rimoldi Francesca Magri Simona Zanotti Laura Napoli Michela Ripolone Serena Pagliarani Patrizia Ciscato Daniele Velardo Adele D’Amico Enrico Bertini Giacomo Pietro Comi Giacomo Pietro Comi Dario Ronchi Dario Ronchi Stefania Corti Stefania Corti |
| author_sort | Daniela Piga |
| collection | DOAJ |
| description | BackgroundCongenital myopathies are a group of heterogeneous inherited disorders, mainly characterized by early-onset hypotonia and muscle weakness. The spectrum of clinical phenotype can be highly variable, going from very mild to severe presentations. The course also varies broadly resulting in a fatal outcome in the most severe cases but can either be benign or lead to an amelioration even in severe presentations. Muscle biopsy analysis is crucial for the identification of pathognomonic morphological features, such as core areas, nemaline bodies or rods, nuclear centralizations and congenital type 1 fibers disproportion. However, multiple abnormalities in the same muscle can be observed, making more complex the myopathological scenario.Case presentationHere, we describe an Italian newborn presenting with severe hypotonia, respiratory insufficiency, inability to suck and swallow, requiring mechanical ventilation and gastrostomy feeding. Muscle biopsy analyzed by light microscopy showed the presence of vacuoles filled with glycogen, suggesting a metabolic myopathy, but also fuchsinophilic inclusions. Ultrastructural studies confirmed the presence of normally structured glycogen, and the presence of minirods, directing the diagnostic hypothesis toward a nemaline myopathy. An expanded Next Generation Sequencing analysis targeting congenital myopathies genes revealed the presence of a novel heterozygous c.965 T > A p. (Leu322Gln) variant in the ACTA1 gene, which encodes the skeletal muscle alpha-actin.ConclusionOur case expands the repertoire of molecular and pathological features observed in actinopathies. We highlight the value of ultrastructural examination to investigate the abnormalities detected at the histological level. We also emphasized the use of expanded gene panels in the molecular analysis of neuromuscular patients, especially for those ones presenting multiple bioptic alterations. |
| first_indexed | 2024-03-07T16:22:48Z |
| format | Article |
| id | doaj.art-8fb71253fe8941deace9208bc912160a |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-03-07T16:22:48Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-8fb71253fe8941deace9208bc912160a2024-03-04T04:17:26ZengFrontiers Media S.A.Frontiers in Neurology1664-22952024-03-011510.3389/fneur.2024.13406931340693Case report: A novel ACTA1 variant in a patient with nemaline rods and increased glycogen depositionDaniela Piga0Martina Rimoldi1Martina Rimoldi2Francesca Magri3Simona Zanotti4Laura Napoli5Michela Ripolone6Serena Pagliarani7Patrizia Ciscato8Daniele Velardo9Adele D’Amico10Enrico Bertini11Giacomo Pietro Comi12Giacomo Pietro Comi13Dario Ronchi14Dario Ronchi15Stefania Corti16Stefania Corti17IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, ItalyIRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Neuromuscular and Rare Disease Unit, Milan, ItalyIRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Medical Genetics Unit, Milan, ItalyIRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, ItalyIRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Neuromuscular and Rare Disease Unit, Milan, ItalyIRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Neuromuscular and Rare Disease Unit, Milan, ItalyIRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Neuromuscular and Rare Disease Unit, Milan, ItalyIRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, ItalyIRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Neuromuscular and Rare Disease Unit, Milan, ItalyIRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Neuromuscular and Rare Disease Unit, Milan, ItalyUnit of Neuromuscular and Neurodegenerative Disorders, Bambino Gesu’ Children’s Research Hospital, IRCCS, Rome, ItalyUnit of Neuromuscular and Neurodegenerative Disorders, Bambino Gesu’ Children’s Research Hospital, IRCCS, Rome, ItalyIRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, ItalyDepartment of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, Milan, ItalyIRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, ItalyDepartment of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, Milan, ItalyIRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Neuromuscular and Rare Disease Unit, Milan, ItalyDepartment of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, Milan, ItalyBackgroundCongenital myopathies are a group of heterogeneous inherited disorders, mainly characterized by early-onset hypotonia and muscle weakness. The spectrum of clinical phenotype can be highly variable, going from very mild to severe presentations. The course also varies broadly resulting in a fatal outcome in the most severe cases but can either be benign or lead to an amelioration even in severe presentations. Muscle biopsy analysis is crucial for the identification of pathognomonic morphological features, such as core areas, nemaline bodies or rods, nuclear centralizations and congenital type 1 fibers disproportion. However, multiple abnormalities in the same muscle can be observed, making more complex the myopathological scenario.Case presentationHere, we describe an Italian newborn presenting with severe hypotonia, respiratory insufficiency, inability to suck and swallow, requiring mechanical ventilation and gastrostomy feeding. Muscle biopsy analyzed by light microscopy showed the presence of vacuoles filled with glycogen, suggesting a metabolic myopathy, but also fuchsinophilic inclusions. Ultrastructural studies confirmed the presence of normally structured glycogen, and the presence of minirods, directing the diagnostic hypothesis toward a nemaline myopathy. An expanded Next Generation Sequencing analysis targeting congenital myopathies genes revealed the presence of a novel heterozygous c.965 T > A p. (Leu322Gln) variant in the ACTA1 gene, which encodes the skeletal muscle alpha-actin.ConclusionOur case expands the repertoire of molecular and pathological features observed in actinopathies. We highlight the value of ultrastructural examination to investigate the abnormalities detected at the histological level. We also emphasized the use of expanded gene panels in the molecular analysis of neuromuscular patients, especially for those ones presenting multiple bioptic alterations.https://www.frontiersin.org/articles/10.3389/fneur.2024.1340693/fullACTA1skeletal muscle rodsglycogen storagenemaline myopathycase report |
| spellingShingle | Daniela Piga Martina Rimoldi Martina Rimoldi Francesca Magri Simona Zanotti Laura Napoli Michela Ripolone Serena Pagliarani Patrizia Ciscato Daniele Velardo Adele D’Amico Enrico Bertini Giacomo Pietro Comi Giacomo Pietro Comi Dario Ronchi Dario Ronchi Stefania Corti Stefania Corti Case report: A novel ACTA1 variant in a patient with nemaline rods and increased glycogen deposition Frontiers in Neurology ACTA1 skeletal muscle rods glycogen storage nemaline myopathy case report |
| title | Case report: A novel ACTA1 variant in a patient with nemaline rods and increased glycogen deposition |
| title_full | Case report: A novel ACTA1 variant in a patient with nemaline rods and increased glycogen deposition |
| title_fullStr | Case report: A novel ACTA1 variant in a patient with nemaline rods and increased glycogen deposition |
| title_full_unstemmed | Case report: A novel ACTA1 variant in a patient with nemaline rods and increased glycogen deposition |
| title_short | Case report: A novel ACTA1 variant in a patient with nemaline rods and increased glycogen deposition |
| title_sort | case report a novel acta1 variant in a patient with nemaline rods and increased glycogen deposition |
| topic | ACTA1 skeletal muscle rods glycogen storage nemaline myopathy case report |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2024.1340693/full |
| work_keys_str_mv | AT danielapiga casereportanovelacta1variantinapatientwithnemalinerodsandincreasedglycogendeposition AT martinarimoldi casereportanovelacta1variantinapatientwithnemalinerodsandincreasedglycogendeposition AT martinarimoldi casereportanovelacta1variantinapatientwithnemalinerodsandincreasedglycogendeposition AT francescamagri casereportanovelacta1variantinapatientwithnemalinerodsandincreasedglycogendeposition AT simonazanotti casereportanovelacta1variantinapatientwithnemalinerodsandincreasedglycogendeposition AT lauranapoli casereportanovelacta1variantinapatientwithnemalinerodsandincreasedglycogendeposition AT michelaripolone casereportanovelacta1variantinapatientwithnemalinerodsandincreasedglycogendeposition AT serenapagliarani casereportanovelacta1variantinapatientwithnemalinerodsandincreasedglycogendeposition AT patriziaciscato casereportanovelacta1variantinapatientwithnemalinerodsandincreasedglycogendeposition AT danielevelardo casereportanovelacta1variantinapatientwithnemalinerodsandincreasedglycogendeposition AT adeledamico casereportanovelacta1variantinapatientwithnemalinerodsandincreasedglycogendeposition AT enricobertini casereportanovelacta1variantinapatientwithnemalinerodsandincreasedglycogendeposition AT giacomopietrocomi casereportanovelacta1variantinapatientwithnemalinerodsandincreasedglycogendeposition AT giacomopietrocomi casereportanovelacta1variantinapatientwithnemalinerodsandincreasedglycogendeposition AT darioronchi casereportanovelacta1variantinapatientwithnemalinerodsandincreasedglycogendeposition AT darioronchi casereportanovelacta1variantinapatientwithnemalinerodsandincreasedglycogendeposition AT stefaniacorti casereportanovelacta1variantinapatientwithnemalinerodsandincreasedglycogendeposition AT stefaniacorti casereportanovelacta1variantinapatientwithnemalinerodsandincreasedglycogendeposition |