Claudio Semplicini1, John Vissing1, Julia R Dahlqvist1, Tanya Stojkovic1, Luca Bello1, Nanna Witting1, Morten Duno1, France Leturcq1, Cinzia Bertolin1, Paola D'Ambrosio1, Bruno Eymard1, Corrado Angelini1, Luisa Politano1, Pascal Laforêt2, Elena Pegoraro2. 1. From the Neuromuscular Center (C.S., L.B., C.B., E.P.), Department of Neurosciences, University of Padova, Italy; the Neuromuscular Clinic and Research Unit (J.V., J.R.D., N.W.), Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark; Paris-Est Neuromuscular Center (T.S., B.E., P.L.), Institut of Myology, Pitié-Salpêtrière Hospital, Paris, France; the Department of Clinical Genetics (M.D.), University of Copenhagen, Rigshospitalet, Denmark; Laboratoire de Biochimie et Génétique Moléculaire (F.L.), Groupe Hospitalier Cochin, Paris, France; Cardiomyology and Medical Genetics (P.D., L.P.), Department of Experimental Medicine, Second University of Naples; and the IRCCS San Camillo (C.A.), Venezia, Italy. 2. From the Neuromuscular Center (C.S., L.B., C.B., E.P.), Department of Neurosciences, University of Padova, Italy; the Neuromuscular Clinic and Research Unit (J.V., J.R.D., N.W.), Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark; Paris-Est Neuromuscular Center (T.S., B.E., P.L.), Institut of Myology, Pitié-Salpêtrière Hospital, Paris, France; the Department of Clinical Genetics (M.D.), University of Copenhagen, Rigshospitalet, Denmark; Laboratoire de Biochimie et Génétique Moléculaire (F.L.), Groupe Hospitalier Cochin, Paris, France; Cardiomyology and Medical Genetics (P.D., L.P.), Department of Experimental Medicine, Second University of Naples; and the IRCCS San Camillo (C.A.), Venezia, Italy. elena.pegoraro@unipd.it pascal.laforet@psl.aphp.fr.
Abstract
OBJECTIVE: To determine the clinical spectrum of limb-girdle muscular dystrophy 2E (LGMD2E) and to investigate whether genetic or biochemical features can predict the phenotype of the disease. METHODS: All LGMD2E patients followed in participating centers were included. A specific clinical protocol was created, including quantitative evaluation of motor, respiratory, and cardiac function. Phenotype was defined as severe or mild if the age at loss of ambulation occurred before or after 18 years. Molecular analysis of SGCB gene and biochemical features of muscle biopsies were reviewed. RESULTS: Thirty-two patients were included (16 male, 16 female; age 7-67 years; 15 severe, 12 mild, and 5 unknown). Neurologic examination showed proximal muscle weakness in all patients, but distal involvement was also observed in patients with severe disease early in the disease course. Cardiac involvement was observed in 20 patients (63%) even before overt muscle involvement. Six patients had restrictive respiratory insufficiency requiring assisted ventilation (19%). Seventeen different mutations were identified, and 3 were recurrent. The c.377_384dup (13 alleles) was associated with the severe form, the c.-22_10dup (10) with the milder form, and the c.341C>T (9) with both. The entire sarcoglycan complex was undetectable by muscle immunohistochemistry or Western blot in 9/10 severe cases and reduced in 7/7 mild cases. The residual amount of sarcoglycan in muscle resulted a predictor of age at loss of ambulation. CONCLUSIONS: This study expands the spectrum of phenotype in β-sarcoglycanopathy and provides strong evidence that severity of clinical involvement may be predicted by SGCB gene mutation and sarcoglycan protein expression.
OBJECTIVE: To determine the clinical spectrum of limb-girdle muscular dystrophy 2E (LGMD2E) and to investigate whether genetic or biochemical features can predict the phenotype of the disease. METHODS: All LGMD2E patients followed in participating centers were included. A specific clinical protocol was created, including quantitative evaluation of motor, respiratory, and cardiac function. Phenotype was defined as severe or mild if the age at loss of ambulation occurred before or after 18 years. Molecular analysis of SGCB gene and biochemical features of muscle biopsies were reviewed. RESULTS: Thirty-two patients were included (16 male, 16 female; age 7-67 years; 15 severe, 12 mild, and 5 unknown). Neurologic examination showed proximal muscle weakness in all patients, but distal involvement was also observed in patients with severe disease early in the disease course. Cardiac involvement was observed in 20 patients (63%) even before overt muscle involvement. Six patients had restrictive respiratory insufficiency requiring assisted ventilation (19%). Seventeen different mutations were identified, and 3 were recurrent. The c.377_384dup (13 alleles) was associated with the severe form, the c.-22_10dup (10) with the milder form, and the c.341C>T (9) with both. The entire sarcoglycan complex was undetectable by muscle immunohistochemistry or Western blot in 9/10 severe cases and reduced in 7/7 mild cases. The residual amount of sarcoglycan in muscle resulted a predictor of age at loss of ambulation. CONCLUSIONS: This study expands the spectrum of phenotype in β-sarcoglycanopathy and provides strong evidence that severity of clinical involvement may be predicted by SGCB gene mutation and sarcoglycan protein expression.
Authors: Serge Herson; Faycal Hentati; Aude Rigolet; Anthony Behin; Norma B Romero; France Leturcq; Pascal Laforêt; Thierry Maisonobe; Rim Amouri; Hafedh Haddad; Muriel Audit; Marie Montus; Carole Masurier; Bernard Gjata; Christophe Georger; Mustapha Cheraï; Pierre Carlier; Jean-Yves Hogrel; Ariane Herson; Yves Allenbach; François M Lemoine; David Klatzmann; H Lee Sweeney; Richard C Mulligan; Bruno Eymard; Didier Caizergues; Thomas Voït; Olivier Benveniste Journal: Brain Date: 2012-01-11 Impact factor: 13.501
Authors: R Barresi; C Di Blasi; T Negri; R Brugnoni; A Vitali; G Felisari; A Salandi; S Daniel; F Cornelio; L Morandi; M Mora Journal: J Med Genet Date: 2000-02 Impact factor: 6.318
Authors: N B Romero; F M Tomé; F Leturcq; F E el Kerch; K Azibi; L Bachner; R D Anderson; S L Roberds; K P Campbell; M Fardeau Journal: C R Acad Sci III Date: 1994-01
Authors: S L Roberds; F Leturcq; V Allamand; F Piccolo; M Jeanpierre; R D Anderson; L E Lim; J C Lee; F M Tomé; N B Romero Journal: Cell Date: 1994-08-26 Impact factor: 41.582
Authors: L Politano; V Nigro; L Passamano; V Petretta; L I Comi; S Papparella; G Nigro; P F Rambaldi; P Raia; A Pini; M Mora; M A Giugliano; M G Esposito; G Nigro Journal: Neuromuscul Disord Date: 2001-03 Impact factor: 4.296
Authors: Eric R Pozsgai; Danielle A Griffin; Kristin N Heller; Jerry R Mendell; Louise R Rodino-Klapac Journal: Mol Ther Date: 2017-03-09 Impact factor: 11.454
Authors: David Israeli; Jérémie Cosette; Guillaume Corre; Fatima Amor; Jérôme Poupiot; Daniel Stockholm; Marie Montus; Bernard Gjata; Isabelle Richard Journal: Mol Ther Methods Clin Dev Date: 2019-05-10 Impact factor: 6.698
Authors: Dimitra G Georganopoulou; Vasilis G Moisiadis; Firhan A Malik; Ali Mohajer; Tanya M Dashevsky; Shirley T Wuu; Chih-Kao Hu Journal: Protein J Date: 2021-06-10 Impact factor: 2.371