Muscle involvement in limb-girdle muscular dystrophy with GMPPB deficiency (LGMD2T)

TY - JOUR

T1 - Muscle involvement in limb-girdle muscular dystrophy with GMPPB deficiency (LGMD2T)

AU - Oestergaard, S T

AU - Stojkovic, T

AU - Dahlqvist, Julia Rebecka

AU - Bouchet-Seraphin, C

AU - Nectoux, J

AU - Leturcq, France

AU - Cossée, M

AU - Solé, G

AU - Thomsen, C

AU - Krag, T O

AU - Vissing, J

PY - 2016/12

Y1 - 2016/12

N2 - Objective: In this study, muscle involvement assessed by MRI and levels of GMPPB and glycosylation of a-dystroglycan expression in muscle were examined in patients with limb-girdle muscular dystrophy (LGMD) type 2T. Methods: Six new patients with genetically verified mutations in GMPPB were studied. T1- weighted magnetic resonance images were obtained in 4 participants. Muscle strength and potential involvement of extramuscular organs were examined. Glycosylation of a-dystroglycan in muscle was studied, and GMPPB and a-dystroglycan expression was analyzed by Western blotting. Prevalence of LGMD2T was calculated from the total LGMD population in Denmark. GMPPB was sequenced in all unclassified cases. Results: Two patients carried 3 new mutations in GMPPB. The other 4 patients carried previously described pathogenic mutations in GMPPB. MRI showed that the paraspinal muscles were the most affected, followed by involvement of hamstrings. Our results showed a loss of glycosylation of a-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.

AB - Objective: In this study, muscle involvement assessed by MRI and levels of GMPPB and glycosylation of a-dystroglycan expression in muscle were examined in patients with limb-girdle muscular dystrophy (LGMD) type 2T. Methods: Six new patients with genetically verified mutations in GMPPB were studied. T1- weighted magnetic resonance images were obtained in 4 participants. Muscle strength and potential involvement of extramuscular organs were examined. Glycosylation of a-dystroglycan in muscle was studied, and GMPPB and a-dystroglycan expression was analyzed by Western blotting. Prevalence of LGMD2T was calculated from the total LGMD population in Denmark. GMPPB was sequenced in all unclassified cases. Results: Two patients carried 3 new mutations in GMPPB. The other 4 patients carried previously described pathogenic mutations in GMPPB. MRI showed that the paraspinal muscles were the most affected, followed by involvement of hamstrings. Our results showed a loss of glycosylation of a-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.

KW - Journal Article

U2 - 10.1212/NXG.0000000000000112

DO - 10.1212/NXG.0000000000000112

M3 - Journal article

C2 - 27766311

SN - 2376-7839

VL - 2

JO - Neurology: Genetics

JF - Neurology: Genetics

IS - 6

M1 - e112

ER -