title: Immunohistochemistry on a panel of Emery-Dreifuss muscular dystrophy samples reveals nuclear envelope proteins as inconsistent markers for pathology.
abstract: Reports of aberrant distribution for some nuclear envelope proteins in cells expressing a few Emery-Dreifuss muscular dystrophy mutations raised the possibility that such protein redistribution could underlie pathology and/or be diagnostic. However, this disorder is linked to 8 different genes encoding nuclear envelope proteins, raising the question of whether a particular protein is most relevant. Therefore, myoblast/fibroblast cultures from biopsy and tissue sections from a panel of nine Emery-Dreifuss muscular dystrophy patients (4 male, 5 female) including those carrying emerin and FHL1 (X-linked) and several lamin A (autosomal dominant) mutations were stained for the proteins linked to the disorder. As tissue-specific nuclear envelope proteins have been postulated to mediate the tissue-specific pathologies of different nuclear envelopathies, patient samples were also stained for several muscle-specific nuclear membrane proteins. Although linked proteins nesprin 1 and SUN2 and muscle-specific proteins NET5/Samp1 and Tmem214 yielded aberrant distributions in individual patient cells, none exhibited defects through the larger patient panel. Muscle-specific Tmem38A normally appeared in both the nuclear envelope and sarcoplasmic reticulum, but most patient samples exhibited a moderate redistribution favouring the sarcoplasmic reticulum. The absence of striking uniform defects in nuclear envelope protein distribution indicates that such staining will be unavailing for general diagnostics, though it remains possible that specific mutations exhibiting protein distribution defects might reflect a particular clinical variant. These findings further argue that multiple pathways can lead to the generally similar pathologies of this disorder while at the same time the different cellular phenotypes observed possibly may help explain the considerable clinical variation of EDMD.
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Phu
authors.initials: P
authors.lastname: Le Thanh
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK; Friedrich-Baur-Institute, Ludwig Maximilian University, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Meinke
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Nadia
authors.initials: N
authors.lastname: Korfali
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Vlastimil
authors.initials: V
authors.lastname: Srsen
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Robson
authors.affiliation: Institute of Human Genetics, University of Greifswald, Greifswald, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Wehnert
authors.affiliation: Friedrich-Baur-Institute, Ludwig Maximilian University, Munich, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Schoser
authors.affiliation: Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children NHS Trust, London, UK.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sewry
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK. Electronic address: e.schirmer@ed.ac.uk.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Schirmer
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000378:metabolism* / Q000473:pathology; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D014015:Tissue Banks
chemical_list: D015415:Biomarkers; D009687:Nuclear Proteins
keywords: Emery–Dreifuss muscular dystrophy; Muscle biopsy; Nuclear envelope; Nuclear envelope transmembrane protein