title: Muscle involvement in limb-girdle muscular dystrophy with GMPPB deficiency (LGMD2T).
abstract: OBJECTIVE
  In this study, muscle involvement assessed by MRI and levels of GMPPB and glycosylation of α-dystroglycan expression in muscle were examined in patients with limb-girdle muscular dystrophy (LGMD) type 2T.
  
  
  METHODS
  Six new patients with genetically verified mutations inGMPPBwere studied. T1-weighted magnetic resonance images were obtained in 4 participants. Muscle strength and potential involvement of extramuscular organs were examined. Glycosylation of α-dystroglycan in muscle was studied, and GMPPB and α-dystroglycan expression was analyzed by Western blotting. Prevalence of LGMD2T was calculated from the total LGMD population in Denmark.GMPPBwas sequenced in all unclassified cases.
  
  
  RESULTS
  Two patients carried 3 new mutations inGMPPB. The other 4 patients carried previously described pathogenic mutations inGMPPB. MRI showed that the paraspinal muscles were the most affected, followed by involvement of hamstrings. Our results showed a loss of glycosylation of α-dystroglycan as well as secondary loss of merosin expression on Western blotting. The prevalence of LGMD2T in the Danish cohort of patients with LGMD is 1.5%.
  
  
  CONCLUSIONS
  The new findings of this study are (1) the consistent finding of a preferential affection of paraspinal and hamstring muscles in LGMD2T, (2) 3 new mutations in GMPPB, (3) variable loss of glycosylation tested with IIH6 and VIA4 antibodies, and (4) a prevalence of LGMD2T of 1.5% in a well-characterized Danish LGMD cohort.
authors.affiliation: Copenhagen Neuromuscular Center (S.T.O., J.R.D., T.O.K., J.V.), Department of Neurology, Department of Diagnostic Radiology (C.T.), Rigshospitalet, University of Copenhagen, Denmark; AP-HP, Institute of Myology (T.S.), Centre de reference des maladies neuromusculaires Paris Est, G-H Pitié-Salpêtrière; AP-HP, Hôpital Bichat (C.B.-S.), Département de Biochimie et de Génétique, Paris; Service de génétique et biologie moléculaires (J.N., F.L.), HUPC Hôpital Cochin, Paris; Laboratoire de Génétique Moléculaire and UE 7402 (M.C.), CHRU Montpellier, Université Montpellier; and Center of Reference for Neuromuscular Disorders (G.S.), CHU Bordeaux, France.
authors.forename: S T
authors.initials: ST
authors.lastname: Oestergaard
authors.affiliation: Copenhagen Neuromuscular Center (S.T.O., J.R.D., T.O.K., J.V.), Department of Neurology, Department of Diagnostic Radiology (C.T.), Rigshospitalet, University of Copenhagen, Denmark; AP-HP, Institute of Myology (T.S.), Centre de reference des maladies neuromusculaires Paris Est, G-H Pitié-Salpêtrière; AP-HP, Hôpital Bichat (C.B.-S.), Département de Biochimie et de Génétique, Paris; Service de génétique et biologie moléculaires (J.N., F.L.), HUPC Hôpital Cochin, Paris; Laboratoire de Génétique Moléculaire and UE 7402 (M.C.), CHRU Montpellier, Université Montpellier; and Center of Reference for Neuromuscular Disorders (G.S.), CHU Bordeaux, France.
authors.forename: T
authors.initials: T
authors.lastname: Stojkovic
authors.affiliation: Copenhagen Neuromuscular Center (S.T.O., J.R.D., T.O.K., J.V.), Department of Neurology, Department of Diagnostic Radiology (C.T.), Rigshospitalet, University of Copenhagen, Denmark; AP-HP, Institute of Myology (T.S.), Centre de reference des maladies neuromusculaires Paris Est, G-H Pitié-Salpêtrière; AP-HP, Hôpital Bichat (C.B.-S.), Département de Biochimie et de Génétique, Paris; Service de génétique et biologie moléculaires (J.N., F.L.), HUPC Hôpital Cochin, Paris; Laboratoire de Génétique Moléculaire and UE 7402 (M.C.), CHRU Montpellier, Université Montpellier; and Center of Reference for Neuromuscular Disorders (G.S.), CHU Bordeaux, France.
authors.forename: J R
authors.initials: JR
authors.lastname: Dahlqvist
authors.affiliation: Copenhagen Neuromuscular Center (S.T.O., J.R.D., T.O.K., J.V.), Department of Neurology, Department of Diagnostic Radiology (C.T.), Rigshospitalet, University of Copenhagen, Denmark; AP-HP, Institute of Myology (T.S.), Centre de reference des maladies neuromusculaires Paris Est, G-H Pitié-Salpêtrière; AP-HP, Hôpital Bichat (C.B.-S.), Département de Biochimie et de Génétique, Paris; Service de génétique et biologie moléculaires (J.N., F.L.), HUPC Hôpital Cochin, Paris; Laboratoire de Génétique Moléculaire and UE 7402 (M.C.), CHRU Montpellier, Université Montpellier; and Center of Reference for Neuromuscular Disorders (G.S.), CHU Bordeaux, France.
authors.forename: C
authors.initials: C
authors.lastname: Bouchet-Seraphin
authors.affiliation: Copenhagen Neuromuscular Center (S.T.O., J.R.D., T.O.K., J.V.), Department of Neurology, Department of Diagnostic Radiology (C.T.), Rigshospitalet, University of Copenhagen, Denmark; AP-HP, Institute of Myology (T.S.), Centre de reference des maladies neuromusculaires Paris Est, G-H Pitié-Salpêtrière; AP-HP, Hôpital Bichat (C.B.-S.), Département de Biochimie et de Génétique, Paris; Service de génétique et biologie moléculaires (J.N., F.L.), HUPC Hôpital Cochin, Paris; Laboratoire de Génétique Moléculaire and UE 7402 (M.C.), CHRU Montpellier, Université Montpellier; and Center of Reference for Neuromuscular Disorders (G.S.), CHU Bordeaux, France.
authors.forename: J
authors.initials: J
authors.lastname: Nectoux
authors.affiliation: Copenhagen Neuromuscular Center (S.T.O., J.R.D., T.O.K., J.V.), Department of Neurology, Department of Diagnostic Radiology (C.T.), Rigshospitalet, University of Copenhagen, Denmark; AP-HP, Institute of Myology (T.S.), Centre de reference des maladies neuromusculaires Paris Est, G-H Pitié-Salpêtrière; AP-HP, Hôpital Bichat (C.B.-S.), Département de Biochimie et de Génétique, Paris; Service de génétique et biologie moléculaires (J.N., F.L.), HUPC Hôpital Cochin, Paris; Laboratoire de Génétique Moléculaire and UE 7402 (M.C.), CHRU Montpellier, Université Montpellier; and Center of Reference for Neuromuscular Disorders (G.S.), CHU Bordeaux, France.
authors.forename: F
authors.initials: F
authors.lastname: Leturcq
authors.affiliation: Copenhagen Neuromuscular Center (S.T.O., J.R.D., T.O.K., J.V.), Department of Neurology, Department of Diagnostic Radiology (C.T.), Rigshospitalet, University of Copenhagen, Denmark; AP-HP, Institute of Myology (T.S.), Centre de reference des maladies neuromusculaires Paris Est, G-H Pitié-Salpêtrière; AP-HP, Hôpital Bichat (C.B.-S.), Département de Biochimie et de Génétique, Paris; Service de génétique et biologie moléculaires (J.N., F.L.), HUPC Hôpital Cochin, Paris; Laboratoire de Génétique Moléculaire and UE 7402 (M.C.), CHRU Montpellier, Université Montpellier; and Center of Reference for Neuromuscular Disorders (G.S.), CHU Bordeaux, France.
authors.forename: M
authors.initials: M
authors.lastname: Cossée
authors.affiliation: Copenhagen Neuromuscular Center (S.T.O., J.R.D., T.O.K., J.V.), Department of Neurology, Department of Diagnostic Radiology (C.T.), Rigshospitalet, University of Copenhagen, Denmark; AP-HP, Institute of Myology (T.S.), Centre de reference des maladies neuromusculaires Paris Est, G-H Pitié-Salpêtrière; AP-HP, Hôpital Bichat (C.B.-S.), Département de Biochimie et de Génétique, Paris; Service de génétique et biologie moléculaires (J.N., F.L.), HUPC Hôpital Cochin, Paris; Laboratoire de Génétique Moléculaire and UE 7402 (M.C.), CHRU Montpellier, Université Montpellier; and Center of Reference for Neuromuscular Disorders (G.S.), CHU Bordeaux, France.
authors.forename: G
authors.initials: G
authors.lastname: Solé
authors.affiliation: Copenhagen Neuromuscular Center (S.T.O., J.R.D., T.O.K., J.V.), Department of Neurology, Department of Diagnostic Radiology (C.T.), Rigshospitalet, University of Copenhagen, Denmark; AP-HP, Institute of Myology (T.S.), Centre de reference des maladies neuromusculaires Paris Est, G-H Pitié-Salpêtrière; AP-HP, Hôpital Bichat (C.B.-S.), Département de Biochimie et de Génétique, Paris; Service de génétique et biologie moléculaires (J.N., F.L.), HUPC Hôpital Cochin, Paris; Laboratoire de Génétique Moléculaire and UE 7402 (M.C.), CHRU Montpellier, Université Montpellier; and Center of Reference for Neuromuscular Disorders (G.S.), CHU Bordeaux, France.
authors.forename: C
authors.initials: C
authors.lastname: Thomsen
authors.affiliation: Copenhagen Neuromuscular Center (S.T.O., J.R.D., T.O.K., J.V.), Department of Neurology, Department of Diagnostic Radiology (C.T.), Rigshospitalet, University of Copenhagen, Denmark; AP-HP, Institute of Myology (T.S.), Centre de reference des maladies neuromusculaires Paris Est, G-H Pitié-Salpêtrière; AP-HP, Hôpital Bichat (C.B.-S.), Département de Biochimie et de Génétique, Paris; Service de génétique et biologie moléculaires (J.N., F.L.), HUPC Hôpital Cochin, Paris; Laboratoire de Génétique Moléculaire and UE 7402 (M.C.), CHRU Montpellier, Université Montpellier; and Center of Reference for Neuromuscular Disorders (G.S.), CHU Bordeaux, France.
authors.forename: T O
authors.initials: TO
authors.lastname: Krag
authors.affiliation: Copenhagen Neuromuscular Center (S.T.O., J.R.D., T.O.K., J.V.), Department of Neurology, Department of Diagnostic Radiology (C.T.), Rigshospitalet, University of Copenhagen, Denmark; AP-HP, Institute of Myology (T.S.), Centre de reference des maladies neuromusculaires Paris Est, G-H Pitié-Salpêtrière; AP-HP, Hôpital Bichat (C.B.-S.), Département de Biochimie et de Génétique, Paris; Service de génétique et biologie moléculaires (J.N., F.L.), HUPC Hôpital Cochin, Paris; Laboratoire de Génétique Moléculaire and UE 7402 (M.C.), CHRU Montpellier, Université Montpellier; and Center of Reference for Neuromuscular Disorders (G.S.), CHU Bordeaux, France.
authors.forename: J
authors.initials: J
authors.lastname: Vissing