Journal article
MLIP causes recessive myopathy with rhabdomyolysis, myalgia and baseline elevated serum creatine kinase
Brain (London, England : 1878), Vol.144(9), pp.2722-2731
10/22/2021
DOI: 10.1093/brain/awab275
PMCID: PMC8536936
PMID: 34581780
Abstract
Striated muscle needs to maintain cellular homeostasis in adaptation to increases in physiological and metabolic demands. Failure to do so can result in rhabdomyolysis. The identification of novel genetic conditions associated with rhabdomyolysis helps to shed light on hitherto unrecognized homeostatic mechanisms. Here we report seven individuals in six families from different ethnic backgrounds with biallelic variants in MLIP, which encodes the muscular lamin A/C-interacting protein, MLIP. Patients presented with a consistent phenotype characterized by mild muscle weakness, exercise-induced muscle pain, variable susceptibility to episodes of rhabdomyolysis, and persistent basal elevated serum creatine kinase levels. The biallelic truncating variants were predicted to result in disruption of the nuclear localizing signal of MLIP. Additionally, reduced overall RNA expression levels of the predominant MLIP isoform were observed in patients' skeletal muscle. Collectively, our data increase the understanding of the genetic landscape of rhabdomyolysis to now include MLIP as a novel disease gene in humans and solidifies MLIP's role in normal and diseased skeletal muscle homeostasis.
Details
- Title: Subtitle
- MLIP causes recessive myopathy with rhabdomyolysis, myalgia and baseline elevated serum creatine kinase
- Creators
- Osorio Lopes Abath Neto - University of Pittsburgh Medical CenterLivija Medne - Children's Hospital of PhiladelphiaSandra Donkervoort - National Institute of Neurological Disorders and StrokeMaria Elena Rodríguez-García - Centro de Investigación Biomédica en RedVéronique Bolduc - National Institute of Neurological Disorders and StrokeYing Hu - National Institute of Neurological Disorders and StrokeEleonora Guadagnin - National Institute of Neurological Disorders and StrokeA Reghan Foley - National Institute of Neurological Disorders and StrokeJohn F Brandsema - Children's Hospital of PhiladelphiaAllan M Glanzman - Children's Hospital of PhiladelphiaGihan I Tennekoon - Children's Hospital of PhiladelphiaMariarita Santi - Children's Hospital of PhiladelphiaJustin H Berger - Children's Hospital of PhiladelphiaLynn A Megeney - Ottawa HospitalHirofumi Komaki - National Center of Neurology and PsychiatryMichio Inoue - National Center of Neurology and PsychiatryFrancisco Javier Cotrina-Vinagre - Grupo de Enfermedades Raras, Mitocondriales y Neuromusculares (ERMN), Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.Aurelio Hernández-Lain - Hospital Universitario 12 De OctubreElena Martin-Hernández - Centro de Investigación Biomédica en RedLinford Williams - Children's Hospital of PittsburghSabine Borell - University of FreiburgDavid Schorling - University of FreiburgKimberly Lin - Children's Hospital of PhiladelphiaKonstantinos Kolokotronis - University of WürzburgUta Lichter-Konecki - Children's Hospital of PittsburghJanbernd Kirschner - University of FreiburgIchizo Nishino - National Center of Neurology and PsychiatryBrenda Banwell - Children's Hospital of PhiladelphiaFrancisco Martínez-Azorín - Centro de Investigación Biomédica en RedPatrick G Burgon - Qatar UniversityCarsten G Bönnemann - National Institute of Neurological Disorders and Stroke
- Resource Type
- Journal article
- Publication Details
- Brain (London, England : 1878), Vol.144(9), pp.2722-2731
- DOI
- 10.1093/brain/awab275
- PMID
- 34581780
- PMCID
- PMC8536936
- NLM abbreviation
- Brain
- ISSN
- 0006-8950
- eISSN
- 1460-2156
- Grant note
- MOP119470 / CIHR
- Language
- English
- Date published
- 10/22/2021
- Academic Unit
- Pathology
- Record Identifier
- 9984277264102771
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