A first missense mutation in the delta sarcoglycan gene associated with a severe phenotype and frequency of limb-girdle muscular dystrophy type 2F (LGMD2F) in Brazilian sarcoglycanopathies.
Our findings demonstrate that, even in the presence of a second disease-causing mutation, the p.S151A mutation in the delta-sarcoglycan gene does not result in cardiomyopathy.
Our results suggest that the p.S151A mutation causes a mild, subclinical phenotype of cardiomyopathy, which is prone to be overseen in patients carrying such sequence variants.
In this study, the potential of the p.S151A mutation to cause DCM was investigated by using two different approaches: (1) engineering and characterization of heterozygous knock-in (S151A-) mice carrying the p.S151A mutation and (2) evaluation of the potential of adeno-associated virus (AAV) 9-based cardiac-specific transfer of p.S151A-mutated Sgcd cDNA to rescue the cardiac phenotype in Sgcd-deficient (Sgcd-null) mice as it has been demonstrated for intact, wild-type Sgcd cDNA.
Moreover, the GATT haplotype in this gene (rs931798, rs140617, rs140616, and rs970476) is associated with lower odds of AMD (adjusted odds ratio (OR) 0.13; 95% CI 0.02⁻0.91; <i>p</i> = 0.041).
We identified a novel missense mutation in exon 6 (p.A131P) of the delta-sarcoglycan gene, which in a homozygous state leads to the clinical picture of a limb girdle muscular dystrophy.
We identified a novel missense mutation in exon 6 (p.A131P) of the delta-sarcoglycan gene, which in a homozygous state leads to the clinical picture of a limb girdle muscular dystrophy.
Positive associations with pediatric BPD and the BDNF gene (Vall66), the GAD1 gene (4s2241165), and the dopamine transporter gene (rs41084) have been reported but none of these associations have been replicated in independent samples.
Positive associations with pediatric BPD and the BDNF gene (Vall66), the GAD1 gene (4s2241165), and the dopamine transporter gene (rs41084) have been reported but none of these associations have been replicated in independent samples.
Upon cyclical cell stretching, cardiac myocytes expressing mutant δ-sarcoglycan R97Q or R71T have increased cell-impermeant dye uptake and undergo contractures at greater frequencies than myocytes expressing normal δ-sarcoglycan.
An association of the rs794316 polymorphism with cancer risk was detected in two genetic models (TT vs. AA: OR = 1.34, 95% CI = 1.03-1.74, P <0.001; TT vs. AT+AA: OR = 1.39, 95% CI = 1.09-1.77, P = 0.01).
An association of the rs794316 polymorphism with cancer risk was detected in two genetic models (TT vs. AA: OR = 1.34, 95% CI = 1.03-1.74, P <0.001; TT vs. AT+AA: OR = 1.39, 95% CI = 1.09-1.77, P = 0.01).
After adjusting for clinical covariates, the G/A genotype of the SGCD gene (rs931798) significantly increases the odds of being diagnosed with AMD in 81% of cases (1.81; 95% CI 1.06⁻3.14; <i>p</i> = 0.031), especially the geographic atrophy phenotype (1.82; 95% CI 1.03⁻3.21; <i>p</i> = 0.038) compared to the G/G homozygous genotype.
Moreover, the GATT haplotype in this gene (rs931798, rs140617, rs140616, and rs970476) is associated with lower odds of AMD (adjusted odds ratio (OR) 0.13; 95% CI 0.02⁻0.91; <i>p</i> = 0.041).