BackgroundThe progressive cardiomyopathy that develops in boys with Duchenne and Becker muscular dystrophy (DMD/BMD) is presumed to be a secondary consequence of the fibrosis within the myocardium. There are only limited data on using parametric imaging in these patients. The purpose of this study was to assess native T1 and extracellular volume (ECV) values in DMD patients.MethodsThe Czech population of males with DMD/BMD was screened. All eligible patients fulfilling the inclusion criteria were included. Forty nine males underwent cardiac magnetic resonance (MR) examination including T1 native and post-contrast mapping measurements. One DMD patient and all BMD patients were excluded from statistical analysis. Three groups were compared – Group D1 - DMD patients without late gadolinium enhancement (LGE) (n = 23), Group D2 - DMD patients with LGE (n = 20), and Group C – gender matched controls (n = 13).ResultsCompared to controls, both DMD groups had prolonged T1 native relaxation time. These results are concordant in all 6 segments as well as in global values (1041 ± 31 ms and 1043 ± 37 ms vs. 983 ± 15 ms, both p < 0.05). Group D2 had significantly increased global ECV (0.28 ± 0.044 vs. 0.243 ± 0.013, p < 0.05) and segmental ECV in inferolateral and anterolateral segments in comparison with controls. The results were also significant after adjustment for subjects’ age.ConclusionDMD males had increased native T1 relaxation time independent of the presence or absence of myocardial fibrosis. Cardiac MR may provide clinically useful information even without contrast media administration.

Danon disease (DD) is an X-linked disorder caused by mutations in the lysosomal-associated membrane protein 2 (LAMP2) gene (Xq24). DD is characterized by cognitive deficit, myopathy, and cardiomyopathy in male patients. The phenotype is variable and mitigated in females. The timely identification of de-novo LAMP2 mutated family members, many of whom are heterozygous females, remains critical for their treatment and family counseling. DD laboratory testing builds on minimally invasive quantification of the LAMP2 protein in white blood cells and characterization of the specific mutation. This integrative approach is particularly helpful when assessing suspect female heterozygotes. LAMP2 exon-copy number variations (eCNVs) were so far reported only in X-hemizygous male DD probands. In heterozygous female DD probands, the wild-type allele may hamper the identification of an eCNV even if it results in the complete abolition of LAMP2 transcription and/or translation. To document the likely underappreciated rate of occurrence and point out numerous potential pitfalls of detection of the LAMP2 eCNVs, we present the first two DD heterozygote female probands who harbor novel multi-exon LAMP2 deletions. Critical for counseling and recurrence prediction, we also highlight the need to search for somatic-germinal mosaicism in DD families.

Congenital nephrotic syndrome (CNS) is a heterogeneous group of diseases with different causes and prognoses. Two thirds of cases of NS in the first year of life are caused by mutations in four genes (NPHS1, NPHS2, WT1, and LAMB2). The mutation of WT1 gene can lead to Denys-Drash syndrome (DDS). We report on female monozygotic twins with CNS presenting at 7 and 8 weeks of age with anuric renal failure. Both twins were treated by peritoneal dialysis. Renal biopsy proved diffuse mesangial sclerosis. Genetic analysis detected a new heterozygote WT1 mutation R434P in both twins. One child developed a unilateral nephroblastoma. Both twins died because of complications of CNS (sepsis and extensive thrombosis of central venous system/sepsis and sudden heart failure) at ages 23 weeks/13.5 months, respectively. DNA analysis showed the same WT1 mutation in the father, who showed at his age of 41 years no clinical consequences of this mutation and no signs of DDS. In conclusion, we report the third family with monozygotic twins with DDS due to WT1 mutation. The DDS has very rapidly led to end-stage renal failure and death in both twins which is in striking contrast to the manifestation in their father.

The 45,X karyotype is associated with the highest prevalence of BAV. Also, the presence of the 45,X cell line in any mosaic karyotype increases the probability of BAV.

Abstract. Ischemic stroke is one of the leading causes of cognitive impairment. Antioxidants may be beneficial in brain diseases in which oxidative stress can be assumed. The effect of two antioxidants, stobadine and its new derivative coded SMe1EC2, was studied on post-ischemic functional recovery in the hippocampus of young and 18-month-old rats. The synaptic transmission was apparently absent after 6-min hypoxia/hypoglycemia in both age groups. Re-oxygenation resulted in negligible functional recovery in untreated slices, yet the presence of pyridoindoles tested elicited improved recovery upon re-oxygenation. SMe1EC2 was found more effective in post-ischemic functional recovery and was further tested in the hippocampus of 15-month-old rats in long-term potentiation (LTP) experiments, a synaptic model of learning and memory mechanisms. In slices of aged rats, 3.5-min hypoxia/hypoglycemia resulted in depression of the LTP induction phase (immediately after high frequency stimulation) and this was prevented in the presence of SMe1EC2 (3 μmol/l). Upon "normoxia", marked amelioration of LTP was recorded in the presence of the antioxidant in about 1.5 order lower concentration. These results suggest a possible application of the pyridoindole in the management of brain ischemia and cognitive impairment.