Type 2I Limb-Girdle Muscular Dystrophy

03/01/2018 - "Corticosteroids may be beneficial for the treatment of LGMD2I and should be further investigated."
11/01/2007 - "Our results provide evidence for an inflammatory involvement in the pathological expression of LGMD2I and open up the possibility that this disorder could be treatable with corticosteroids."
11/01/2015 - "The response to immune therapies suggested a possible inflammatory component associated with the muscular dystrophy and highlighted the potential benefit of corticosteroid treatment in patients with LGMD2I and subacute onset. "

11/02/2023 - "Improved efficacy of FKRP AAV gene therapy by combination with ribitol treatment for LGMD2I."

01/01/2018 - "Dermal fibroblasts obtained from a patient with LGMD2I harboring a fukutin-related protein gene mutation (826C>A; Leu276Ile) and 3 healthy donors were reprogrammed to hiPSCs. "
01/01/2016 - "Mice generated by our lab containing the P448L mutation in the fukutin-related protein gene demonstrate the dystrophic phenotype similar to that of LGMD2I. "
01/01/2016 - "Our goal, therefore, was to quantify gait metrics in the fukutin-related protein P448L mutant (P448L) mouse, a recently developed model for LGMD2i. "
01/01/2014 - "Thirty eight adult ambulant LGMD2I patients (19 male; 19 female) with genetically identical mutations (c.826C>A) in the fukutin-related protein (FKRP) gene were recruited. "
05/01/2011 - "Homozygosity mapping revealed a large homozygous block at the LGMD2I locus, and direct sequencing of FKRP encoding fukutin-related-protein detected the common homozygous c.826 C>A (p.Leu276Ile) mutation. "

11/01/2014 - "To study gene replacement therapy, we generated and characterized a new mouse model of LGMD2I harboring the human mutation leucine 276 to isoleucine (L276I) in the mouse alleles. "
01/01/2019 - "Previous studies of LGMD2i made use of a transgenic mouse model in which a proline-to-leucine (P448L) mutation in fukutin-related protein severely reduces glycosylation of α-dystroglycan. "

07/01/2011 - "Abnormal glycosylation of α-dystroglycan in LGMD2I may interfere with brain development and cognitive performances involving the frontal and posterior parietal regions, but does not result in specific brain MRI abnormalities."
12/01/2007 - "Our data suggest that the UPR response is activated in LGMD2I muscle biopsies, and the observed histopathological and ultrastructural alterations may be related to sarcoplasmic structures involved in FKRP and alpha-dystroglycan metabolism and malfunctioning."
12/01/2005 - "However, the marked reduction of alpha-dystroglycan glycosylation in the muscle of MDC1C and LGMD2I patients suggests a role for FKRP in dystroglycan processing. "
02/01/2004 - "Our data therefore suggest a correlation between a reduction in alpha-dystroglycan, the mutation and the clinical phenotype in MDC1C and LGMD2I which supports the hypothesis that dystroglycan plays a central role in the pathogenesis of these disorders."
02/01/2004 - "Individuals with the milder form of LGMD2I were almost invariably homozygous for the Leu276Ile FKRP mutation and showed a variable but subtle alteration in alpha-dystroglycan immunolabeling. "

08/04/2011 - "Studies of cardiac function have not yet been well-defined in deficiencies of dysferlin (LGMD2B) and fukutin related protein (LGMD2I). "
11/01/2008 - "To identify molecular networks specific to dysferlin-deficient muscle that might explain disease pathogenesis, muscle mRNA profiles from 10 mutation-positive LGMD2B/MM patients were compared with a disease control [LGMD2I; (n = 9)], and normal muscle samples (n = 11). "
02/01/2008 - "LGMD relative frequency was as follows: LGMD1C (caveolin-3) 1.3%; LGMD2A (calpain-3) 28.4%; LGMD2B (dysferlin) 18.7%; LGMD2C (gamma-sarcoglycan) 4.5%; LGMD2D (alpha-sarcoglycan) 8.4%; LGMD2E (beta-sarcoglycan) 4.5%; LGMD2F (delta-sarcoglycan) 0.7%; LGMD2I (Fukutin-related protein) 6.4%; and undetermined 27.1%. "
09/01/2003 - "They are: calpain-3 (LGMD2A), dysferlin (LGMD2B), alpha-sarcoglycan (LGMD2D), beta-sarcoglycan (LGMD2E), gamma-sarcoglycan (LGMD2C), delta-sarcoglycan (LGMD2F), telethonin (LGMD2G), TRIM32 (LGMD2H), fukutin-related protein (LGMD2I) and titin (LGMD2J). "
11/01/2008 - "Here we report muscle histological alterations and the analysis of 11 muscle proteins: dystrophin, four sarcoglycans, calpain 3, dysferlin, telethonin, collagen VI, alpha-DG, and alpha2-laminin, in muscle biopsies from 13 unrelated LGMD2I patients with 10 different FKRP mutations. "

09/01/2012 - "In this detailed muscle biopsy study of a patient with molecularly confirmed diagnosis of limb-girdle muscular dystrophy 2I (LGMD2I) we show some new data, that is the presence of altered expression pattern of costamere components as integrin α7B and integrin β1D associated with vinculin costameric derangement and basal lamina ultrastructural abnormalities as detachments and discontinuities suggesting that different cellular compartments are involved in LGMD2I and the altered basement membrane-plasmalemma-cytoskeleton binding can underlie muscle degeneration."

09/01/2012 - "In this detailed muscle biopsy study of a patient with molecularly confirmed diagnosis of limb-girdle muscular dystrophy 2I (LGMD2I) we show some new data, that is the presence of altered expression pattern of costamere components as integrin α7B and integrin β1D associated with vinculin costameric derangement and basal lamina ultrastructural abnormalities as detachments and discontinuities suggesting that different cellular compartments are involved in LGMD2I and the altered basement membrane-plasmalemma-cytoskeleton binding can underlie muscle degeneration."

01/01/2019 - "Previous studies of LGMD2i made use of a transgenic mouse model in which a proline-to-leucine (P448L) mutation in fukutin-related protein severely reduces glycosylation of α-dystroglycan. "

11/01/2014 - "To study gene replacement therapy, we generated and characterized a new mouse model of LGMD2I harboring the human mutation leucine 276 to isoleucine (L276I) in the mouse alleles. "

01/02/2007 - "Endurance training: an effective and safe treatment for patients with LGMD2I."
01/02/2007 - "Moderate-intensity endurance training is a safe method to increase exercise performance and daily function in patients with LGMD2I."

12/01/2017 - "More importantly, the results identified several functional markers of disease pathophysiology that could aid in developing and assessment of novel therapeutics for LGMD2i and possibly other dystroglycanopathies as well. "
01/01/2011 - "Furthermore, the restoration of about 25% of the normal FKRP level could be sufficient for LGMD2I therapy to correct the genetic deficiency effectively and prevent dystrophic pathology."
11/01/2015 - "The response to immune therapies suggested a possible inflammatory component associated with the muscular dystrophy and highlighted the potential benefit of corticosteroid treatment in patients with LGMD2I and subacute onset. "
11/01/2014 - "To study gene replacement therapy, we generated and characterized a new mouse model of LGMD2I harboring the human mutation leucine 276 to isoleucine (L276I) in the mouse alleles. "

02/01/2008 - "Heart transplantation in a child with LGMD2I presenting as isolated dilated cardiomyopathy."