Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome

Moghadaszadeh, Behzad; Petit, Nathalie; Jaillard, C.; Brockington, M; Roy, Susana Quijano; Merlini, Luciano; Romero, Norma B.; Estournet, B.; Desguerre, Isabelle; Chaigne, Denys; Muntoni, Francesco; Topaloǧlu, Haluk; Guicheney, Pascale

doi:10.1038/ng713

Cited by 335 publications

(230 citation statements)

References 12 publications

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“…rigid spine Cmd Pathogenesis rigid spine syndrome CMD is characterized by marked limitation in the flexion of the spine, gradual development of scoliosis leading to reduced respiratory vital capacity and respiratory failure as well as joints contractures. In 2001, Moghadaszadeh et al 9 identified the sePN1 gene and several mutations resulting in rigid spine CMD, suggesting that selenoprotein N can be involved in redox reactions into the cell, protecting it from oxidant damage. Petit et al 186 demonstrated that sePN1 is a glycoprotein-localized within the endoplasmic reticulum that is more abundant in human fetal tissues than in adult ones, including skeletal muscle.…”

Section: Therapeutic Perspectivesmentioning

confidence: 99%

Congenital muscular dystrophy. Part II: a review of pathogenesis and therapeutic perspectives

Reed

2009

Arq. Neuro-Psiquiatr.

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-The congenital muscular dystrophies (CMDs) are a group of genetically and clinically heterogeneous hereditary myopathies with preferentially autosomal recessive inheritance, that are characterized by congenital hypotonia, delayed motor development and early onset of progressive muscle weakness associated with dystrophic pattern on muscle biopsy. The clinical course is broadly variable and can comprise the involvement of the brain and eyes. From 1994, a great development in the knowledge of the molecular basis has occurred and the classification of CMDs has to be continuously up dated. In the last number of this journal, we presented the main clinical and diagnostic data concerning the different subtypes of CMD. In this second part of the review, we analyse the main reports from the literature concerning the pathogenesis and the therapeutic perspectives of the most common subtypes of CMD: MDC1A with merosin deficiency, collagen VI related CMDs (Ullrich and Bethlem), CMDs with abnormal glycosylation of alpha-dystroglycan (Fukuyama CMD, Muscleeye-brain disease, Walker Warburg syndrome, MDC1C, MDC1D), and rigid spine syndrome, another much rare subtype of CMDs not related with the dystrophin/glycoproteins/extracellular matrix complex.Key WorDs: congenital muscular dystrophy, MDC1A, collagen VI related disorders, glycosylation of alphadystroglycan, Fukuyama DMC, muscle-eye-brain (MeB) disease, Walker-Warburg syndrome, rigid spine syndrome. distrofia muscular congênita. parte ii: revisão da patogênese e perspectivas terapêuticas resumo -As distrofias musculares congênitas (DMCs) são miopatias hereditárias geralmente, porém não exclusivamente, de herança autossômica recessiva, que apresentam grande heterogeneidade genética e clínica. são caracterizadas por hipotonia muscular congênita, atraso do desenvolvimento motor e fraqueza muscular de início precoce associada a padrão distrófico na biópsia muscular. o quadro clínico, de gravidade variável, pode também incluir anormalidades oculares e do sistema nervoso central. A partir de 1994, os conhecimentos sobre genética e biologia molecular das DMCs progrediram rapidamente, sendo a classificação continuamente atualizada. os aspectos clínicos e diagnósticos dos principais subtipos de DMC foram apresentados no número anterior deste periódico, como primeira parte desta revisão. Nesta segunda parte apresentaremos os principais mecanismos patogênicos e as perspectivas terapêuticas dos subtipos mais comuns de DMC: DMC tipo 1A com deficiência de merosina, DMCs relacionadas com alterações do colágeno VI (Ullrich e Bethlem), e DMCs com anormalidades de glicosilação da alfa-distroglicana (DMC Fukuyama, DMC "Muscle-eye-brain" ou MeB, síndrome de Walker Warburg, DMC tipo 1C, DMC tipo 1D). A DMC com espinha rígida, mais rara e não relacionada com alterações do complexo distrofina-glicoproteínas associadas-matriz extracelular também será abordada quanto aos mesmos aspectos patogênicos e terapêuticos.PAlAVrAs-ChAVes: distrofia muscular congênita, merosina, colágeno VI, glicosila...

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Section: Therapeutic Perspectivesmentioning

confidence: 99%

Congenital muscular dystrophy. Part II: a review of pathogenesis and therapeutic perspectives

Reed

2009

Arq. Neuro-Psiquiatr.

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“…Genetic deficiency of selenoprotein N (SePN) in humans results in rigid spine muscular dystrophy, multiminicore disease, or desmin-related myopathy with Mallory body-like inclusions (45,46). To date, SePN is the only selenoprotein known to be involved in a human genetic disorder, but no targeted mutation in mice has been reported and mechanistic details of its function are missing.…”

Section: Other Selenoproteinsmentioning

confidence: 99%

New insights into the physiological actions of selenoproteins from genetically modified mice

Schweizer

Schomburg

2005

IUBMB Life (International Union of Biochemistry and Molecular B

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SummarySelenium (Se) is an essential trace element in mammals. Dietary Se restriction or conditions of Se malabsorption lead to deficiency syndromes or exacerbate established diseases in humans and in many animal models. It is assumed that most, if not all, physiological actions of Se are mediated by selenocysteine (Sec) containing proteins. However, the exact role of particular selenoproteins for certain molecular pathways, for the metabolism of nutrients, hormones or cellular components and for the development and adaptive responses of the organism have often remained elusive. Through the use of transgenic animals, it becomes increasingly feasible to interfere specifically with the expression of single selenoproteins in certain tissues or at certain times. While some transgenic animals exhibit phenotypes that were expected from biochemical studies, in other instances the observed effects were a surprise in view of earlier hypotheses. IUBMB Life, 57: 737 -744, 2005

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“…These include rigid-spine muscular dystrophy, multiminicore disease, and Mallory body-like desmin-related myopathy, and are collectively referred to as SEPN-related myopathies. Several pathologic SEPN1 mutations within the coding region and the 5ЈUTR, and also within the SECIS element (discussed earlier), have been identified in patients with SEPN-related myopathies (105,230). However, the underlying molecular mechanisms behind the SelN-dependent myopathies are poorly understood because the functional characterization of this protein is lagging behind.…”

Section: F Selenoprotein Nmentioning

confidence: 99%

“…SelN is the only selenoprotein so far directly linked to a disease (230,265), and unlike the other selenoproteins, its characterization started with a known loss-of-function phenotype. Several forms of early-onset myopathies characterized by hypotonia, weakness, axial muscle impairment, spinal rigidity and life-threatening respiratory failure have been linked to the SelN gene (SEPN1) locus (265).…”

Section: F Selenoprotein Nmentioning

confidence: 99%

Untitled

2007

Antioxidants & Redox Signaling

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Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome

Cited by 335 publications

References 12 publications

Congenital muscular dystrophy. Part II: a review of pathogenesis and therapeutic perspectives

Congenital muscular dystrophy. Part II: a review of pathogenesis and therapeutic perspectives

New insights into the physiological actions of selenoproteins from genetically modified mice

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