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 ?-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 ?-dystroglycan in muscle was studied, and GMPPB and ?-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 ?-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.

SUBMITTER: Oestergaard ST 

PROVIDER: S-EPMC5061416 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature