Desmin-related myopathy with mallory body–like inclusions is caused by mutations of the selenoprotein N gene†
Corresponding Author
Ana Ferreiro MD, PhD
Institut National de la Santé et de la Recherche Médicale U582, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
INSERM U582, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, 47 Bd. de l'Hôpital, 75651 Paris, FranceSearch for more papers by this authorChantal Ceuterick-de Groote PhD
Department of Neuropathology, Born-Bunge Foundation and University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorJared J. Marks BA
Children's Hospital of Philadelphia, Philadelphia, PA
Search for more papers by this authorNathalie Goemans MD
Department of Paediatrics, University Hospital Gasthuisberg, Leuven, Belgium
Search for more papers by this authorGudrun Schreiber MD
Abteilung Neuropädiatrie, Kinderklinik and Poliklinik, Georg-August Universität Göttingen, Göttingen, Germany
Search for more papers by this authorFolker Hanefeld MD
Abteilung Neuropädiatrie, Kinderklinik and Poliklinik, Georg-August Universität Göttingen, Göttingen, Germany
Search for more papers by this authorMichel Fardeau MD
Institut National de la Santé et de la Recherche Médicale U582, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
Search for more papers by this authorJean-Jacques Martin MD, PhD
Department of Neuropathology, Born-Bunge Foundation and University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorHans H. Goebel MD
Department of Neuropathology, Johannes Gutenberg University, Mainz, Germany
Search for more papers by this authorPascale Richard PhD
Service de Biochimie B, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
Search for more papers by this authorPascale Guicheney PhD
Institut National de la Santé et de la Recherche Médicale U582, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
Search for more papers by this authorCarsten G. Bönnemann MD
Children's Hospital of Philadelphia, Philadelphia, PA
Search for more papers by this authorCorresponding Author
Ana Ferreiro MD, PhD
Institut National de la Santé et de la Recherche Médicale U582, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
INSERM U582, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, 47 Bd. de l'Hôpital, 75651 Paris, FranceSearch for more papers by this authorChantal Ceuterick-de Groote PhD
Department of Neuropathology, Born-Bunge Foundation and University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorJared J. Marks BA
Children's Hospital of Philadelphia, Philadelphia, PA
Search for more papers by this authorNathalie Goemans MD
Department of Paediatrics, University Hospital Gasthuisberg, Leuven, Belgium
Search for more papers by this authorGudrun Schreiber MD
Abteilung Neuropädiatrie, Kinderklinik and Poliklinik, Georg-August Universität Göttingen, Göttingen, Germany
Search for more papers by this authorFolker Hanefeld MD
Abteilung Neuropädiatrie, Kinderklinik and Poliklinik, Georg-August Universität Göttingen, Göttingen, Germany
Search for more papers by this authorMichel Fardeau MD
Institut National de la Santé et de la Recherche Médicale U582, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
Search for more papers by this authorJean-Jacques Martin MD, PhD
Department of Neuropathology, Born-Bunge Foundation and University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorHans H. Goebel MD
Department of Neuropathology, Johannes Gutenberg University, Mainz, Germany
Search for more papers by this authorPascale Richard PhD
Service de Biochimie B, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
Search for more papers by this authorPascale Guicheney PhD
Institut National de la Santé et de la Recherche Médicale U582, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
Search for more papers by this authorCarsten G. Bönnemann MD
Children's Hospital of Philadelphia, Philadelphia, PA
Search for more papers by this authorAccession numbers are listed in the Appendix on the last page of this article.
Abstract
Desmin-related myopathies (DRMs) are a heterogeneous group of muscle disorders, morphologically defined by intrasarcoplasmic aggregates of desmin. Mutations in the desmin and the α-B crystallin genes account for approximately one third of the DRM cases. The genetic basis of the other forms remain unknown, including the early-onset, recessive form with Mallory body–like inclusions (MB-DRMs), first described in five related German patients. Recently, we identified the selenoprotein N gene (SEPN1) as responsible for SEPN-related myopathy (SEPN-RM), a unique early-onset myopathy formerly divided in two different nosological categories: rigid spine muscular dystrophy and the severe form of classical multiminicore disease. The finding of Mallory body–like inclusions in two cases of genetically documented SEPN-RM led us to suspect a relationship between MB-DRM and SEPN1. In the original MB-DRM German family, we demonstrated a linkage of the disease to the SEPN1 locus (1p36), and subsequently a homozygous SEPN1 deletion (del 92 nucleotide −19/+73) in the affected patients. A comparative reevaluation showed that MB-DRM and SEPN-RM share identical clinical features. Therefore, we propose that MB-DRM should be categorized as SEPN-RM. These findings substantiate the molecular heterogeneity of DRM, expand the morphological spectrum of SEPN-RM, and implicate a necessary reassessment of the nosological boundaries in early-onset myopathies. Ann Neurol 2004
References
- 1 Goebel HH, Warlo I. Gene-related protein surplus myopathies. Mol Genet Metab 2000; 71: 267–275.
- 2 Nakano S, Engel AG, Akiguchi I, et al. Myofibrillar myopathy. III. Abnormal expression of cyclin-dependent kinases and nuclear proteins. J Neuropathol Exp Neurol 1997; 56: 850–856.
- 3 Nakano S, Engel AG, Waclawik AJ, et al. Myofibrillar myopathy with abnormal foci of desmin positivity. I. Light and electron microscopy analysis of 10 cases. J Neuropathol Exp Neurol 1996; 55: 549–562.
- 4 De Bleecker JL, Engel AG, Ertl BB. Myofibrillar myopathy with abnormal foci of desmin positivity. II. Immunocytochemical analysis reveals accumulation of multiple other proteins. J Neuropathol Exp Neurol 1996; 55: 563–577.
- 5 Engel AG. Myofibrillar myopathy. Ann Neurol 1999; 46: 681–683.
- 6 Goldfarb LG, Park KY, Cervenakova L, et al. Missense mutations in desmin associated with familial cardiac and skeletal myopathy. Nat Genet 1998; 19: 402–403.
- 7 Goebel HH, Fardeau M. Desmin–protein surplus myopathies. 96th European Neuromuscular Centre (ENMC)–sponsored International Workshop held 14–16 September 2001, Naarden, The Netherlands. Neuromuscul Disord 2002; 12: 687–692.
- 8 Fardeau M, Godet-Guillain J, Tomé FM, et al. [A new familial muscular disorder demonstrated by the intra-sarcoplasmic accumulation of a granulo-filamentous material which is dense on electron microscopy (author's transl)]. Rev Neurol (Paris) 1978; 134: 411–425.
- 9 Rappaport L, Contard F, Samuel JL, et al. Storage of phosphorylated desmin in a familial myopathy. FEBS Lett 1988; 231: 421–425.
- 10 Vicart P, Caron A, Guicheney P, et al. A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. Nat Genet 1998; 20: 92–95.
- 11 Goebel HH, Fardeau M. Desminopathies. In: AEH Emery, ed. Diagnostic criteria for neuromuscular disorders. 2nd ed. London: The Royal Society of Medicine Press, 1998: 75–79.
- 12 Goebel HH, Lenard HG, Langenbeck U, et al. A form of congenital muscular dystrophy. Brain Dev 1980; 2: 387–400.
- 13 Fidzianska A, Goebel HH, Osborn M, et al. Mallory body-like inclusions in a hereditary congenital neuromuscular disease. Muscle Nerve 1983; 6: 195–200.
- 14 Fidzianska A, Ryniewicz B, Barcikowska M, et al. A new familial congenital myopathy in children with desmin and dystrophin reacting plaques. J Neurol Sci 1995; 131: 88–95.
- 15 Mallory F. Cirrhosis of the liver: five different lesions from which it may arise. Bull Johns Hopkins Hosp 1911; 22: 69–75.
- 16 Bianchi L, Winckler K, Mihatsch M, et al. Mallory bodies and giant mitochondria—two different structures in liver biopsies from alcoholics. Beitr Pathol 1973; 150: 298–310.
- 17 Goebel HH. Desmin-related myopathies. Curr Opin Neurol 1997; 10: 426–429.
- 18 Lescure A, Gautheret D, Carbon P, et al. Novel selenoproteins identified in silico and in vivo by using a conserved RNA structural motif. J Biol Chem 1999; 274: 38147–38154.
- 19 Moghadaszadeh B, Petit N, Jaillard C, et al. Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome. Nat Genet 2001; 29: 17–18.
- 20 Ferreiro A, Quijano-Roy S, Pichereau C, et al. Mutations of the selenoprotein N gene, implicated in rigid spine muscular dystrophy, cause the classical phenotype of multi-minicore disease. Reassessing the nosology of early-onset myopathies. Am J Hum Genet 2002; 71: 739–749.
- 21 Ferreiro A, Estournet B, Chateau D, et al. Multi-minicore disease—searching for boundaries: phenotype analysis of 38 cases. Ann Neurol 2000; 48: 745–757.
- 22 Flanigan KM, Kerr L, Bromberg MB, et al. Congenital muscular dystrophy with rigid spine syndrome: a clinical, pathological, radiological, and genetic study. Ann Neurol 2000; 47: 152–161.
- 23 Bönnemann CG, Thompson TG, van der Ven PF, et al. Filamin C accumulation is a strong but nonspecific immunohistochemical marker of core formation in muscle. J Neurol Sci 2003; 206: 71–78.
- 24 Ceuterick C, Martin J. Sporadic early adult-onset distal myopathy with rimmed vacuoles: immunohistochemistry and electron microscopy. J Neurol Sci 1996; 139: 190–196.
- 25 Louis DN, von Deimling A, Seizinger BR. A (CA)n dinucleotide repeat assay for evaluating loss of allelic heterozygosity in small and archival human brain tumor specimens. Am J Pathol 1992; 141: 777–782.
- 26 Moghadaszadeh B, Desguerre I, Topaloglu H, et al. Identification of a new locus for a peculiar form of congenital muscular dystrophy with early rigidity of the spine on chromosome 1p35–36. Am J Hum Genet 1998; 62: 1439–1445.
- 27 Ellis FR. European malignant hyperpyrexia group. Br J Anaesth 1984; 56: 1181–1182.
- 28 Goebel HH. Desmin-related neuromuscular disorders. Muscle Nerve 1995; 18: 1306–1320.
- 29 Amato AA, Kagan-Hallet K, Jackson CE, et al. The wide spectrum of myofibrillar myopathy suggests a multifactorial etiology and pathogenesis. Neurology 1998; 51: 1646–1655.
- 30 Goebel HH, Fardeau M. Desmin in myology. 24th European Neuromuscular Center–sponsored workshop held 5–6 November 1993, Naarden, The Netherlands. Neuromuscul Disord 1995; 5: 161–166.
- 31 Goebel HH, Fardeau M. Familial desmin-related myopathies and cardiomyopathies—from myopathology to molecular and clinical genetics. 36th European Neuromuscular Center (ENMC)–sponsored International Workshop 20–22 October, 1995, Naarden, The Netherlands. Neuromuscul Disord 1996; 6: 383–388.
- 32 Goebel HH. Congenital myopathies with inclusion bodies: a brief review. Neuromuscul Disord 1998; 8: 162–168.
- 33 Engel WK. The essentiality of histo- and cytochemical studies of skeletal muscle in the investigation of neuromuscular disease. Neurology 1962; 12: 778.
- 34 Goebel HH, Schloon H, Lenard HG. Congenital myopathy with cytoplasmic bodies. Neuropediatrics 1981; 12: 166–180.
- 35 Brooke MH, Neville HE. Reducing body myopathy. Neurology 1972; 22: 829–840.
- 36 Tomé FM, Fardeau M. Congenital myopathy with “reducing bodies” in muscle fibres. Acta Neuropathol (Berl) 1975; 31: 207–217.
- 37 Bertini E, Salviati G, Apollo F, et al. Reducing body myopathy and desmin storage in skeletal muscle: morphological and biochemical findings. Acta Neuropathol (Berl) 1994; 87: 106–112.
- 38 Goebel HH, Halbig LE, Goldfarb L, et al. Reducing body myopathy with cytoplasmic bodies and rigid spine syndrome: a mixed congenital myopathy. Neuropediatrics 2001; 32: 196–205.
- 39 Sabatelli M, Bertini E, Ricci E, et al. Peripheral neuropathy with giant axons and cardiomyopathy associated with desmin type intermediate filaments in skeletal muscle. J Neurol Sci 1992; 109: 1–10.
- 40 Schröder JM, Sommer C, Schmidt B. Desmin and actin associated with cytoplasmic bodies in skeletal muscle fibers: immunocytochemical and fine structural studies, with a note on unusual 18- to 20-nm filaments. Acta Neuropathol (Berl) 1990; 80: 406–414.
- 41 Mercuri E, Talim B, Moghadaszadeh B, et al. Clinical and imaging findings in 6 cases of congenital muscular dystrophy with rigid spine syndrome linked to chromosome 1p (RSMD1). Neuromuscul Disord 2002; 12: 631–638.
- 42 Petit N, Lescure A, Rederstorff M, et al. Selenoprotein N: an endoplasmic reticulum glycoprotein with an early developmental expression pattern. Hum Mol Genet 2003; 12: 1045–1053.
- 43 Lazarides E. Intermediate filaments as mechanical integrators of cellular space. Nature 1980; 283: 249–256.
- 44 Fridén J, Sjöström M, Ekblom B. Muscle fibre type characteristics in endurance trained and untrained individuals. Eur J Appl Physiol 1984; 52: 266–271.
Citing Literature
