LDLR promoter variant and exon 14 mutation on the same chromosome are associated with an unusually severe FH phenotype and treatment resistance

Familial hypercholesterolemia (FH) is the most common form of autosomal-dominant hypercholesterolemia, and is caused by mutations in the low-density lipoprotein receptor (LDLR) gene. Heterozygous FH is characterized by elevated low-density lipoprotein (LDL) cholesterol and early-onset cardiovascular disease, whereas homozygous FH results in more severe LDL cholesterol elevation with death by 20 years of age. We present here the case of an African-American female FH patient presenting with a myocardial infarction at the age of 48, recurrent angina pectoris and numerous coronary artery stents. Her pretreated LDL cholesterol levels were more typical of a homozygous FH pattern and she was resistant to conventional lipid-lowering treatment, yet her other clinical parameters were not necessarily consistent with homozygous FH. Genetic testing revealed two LDLR variants on the same chromosome: one a novel missense mutation in exon 14 (Cys681Gly) and the other a promoter variant (IVS1-217C>T) previously shown to result in increased LDLR transcription. Disease-associated PCSK9 or APOB mutations were not identified in this individual. Overall, her genetic and clinical profile suggests that enhanced expression of the mutant LDLR allele resulted in a severe phenotype with characteristics of both heterozygous and homozygous FH

Acute and Time-Course Effects of Traditional and Dynamic Warm-Up Routines in Young Elite Junior Tennis Players

Despite the large number of studies that have examined the acute effects of different warm up modalities (WU) on physical performance, none of them have documented the time course of potential performance recovery in tennis players. The aim of this study was twofold: (a) to analyze and compare the acute effects of two different WU modalities (traditional WU [TWU] and dynamic WU [DWU]) on physical performance (i.e., CMJ, sprint, serve speed and accuracy) in elite junior players, as well as (b) to monitor the time course of any WU-induced changes after 30 and 60 min of simulated match-play. Twelve junior elite players completed both WUs modalities (TWU and DWU) in a counterbalanced order on separate days. In each experimental session, counter movement jump (CMJ), 20-m sprint, tennis serve speed and accuracy tests were performed before (immediately after TWU or DWU) during (30 min) and after 60 min of a simulated match play. Measures were compared via four factorial (WU intervention and time) repeated measures ANOVAs. There were main effects of WU (TWU and DWU) throughout the time for all the variables analysed. The results indicate that DWU routine led to significantly faster 20 m sprint times and higher CMJs as well as faster and more accurate tennis serves at both post warm-up and 30 min match-play testing moments in comparison with the scores reported by the TWU routine (p 75-99%). No significant intergroup differences were found at 60-min match-play testing moment in any variable (except for the 20 m sprint). Therefore, the findings of this study recommend for optimal performance in these elite tennis players, DWU routines should be performed prior to formal training and competition rather than TWU routines