RNA analysis of consensus sequence splicing mutations: implications for thediagnosis of Wilson disease

Wilson disease (WD) is an autosomal recessive disorder caused by a defective function of the copper-transporting ATP7B protein. This results in progressive copper overload and consequent liver, brain, and kidney damage. Approximately 300 WD-causing mutations have been described to date. Missense mutations are largely prevalent, while splice-site mutations are rarer. Of these, only a minority are detected in splicing consensus sequences. Further, few splicing mutations have been studied at the RNA level. In this study we report the RNA molecular characterization of three consensus splice-site mutations identified by DNA analysis in WD patients. One of them, c.51 + 4 A --> T, resides in the consensus sequence of the donor splice site of intron 1; the second, c. 2121 + 3 A --> G, occurred in position + 3 of intron 7; and the c.2447 + 5 G --> A is localized in the consensus sequence of the donor splice site of intron 9. Analysis revealed predominantly abnormal splicing in the samples carrying mutations compared to the normal controls. These results strongly suggest that consensus sequence splice-site mutations result in disease by interfering with the production of the normal WD protein. Our data contribute to understanding the mutational spectrum that affect splicing and improve our capability in WD diagnosis

Delayed diagnosis of coeliac disease increases cancer risk

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The Association of Left Ventricular Hypertrophy with Metabolic Syndrome is Dependent on Body Mass Index in Hypertensive Overweight or Obese Patients

Overweight (Ow) and obesity (Ob) influence blood pressure (BP) and left ventricular hypertrophy (LVH). It is unclear whether the presence of metabolic syndrome (MetS) independently affects echocardiographic parameters in hypertension.380 Ow/Ob essential hypertensive patients (age ≤ 65 years) presenting for referred BP control-related problems. MetS was defined according to NCEP III/ATP with AHA modifications and LVH as LVM/h(2.7) ≥ 49.2 g/m(2.7) in males and ≥ 46.7 g/m(2.7) in females. Treatment intensity score (TIS) was used to control for BP treatment as previously reported.Hypertensive patients with MetS had significantly higher BMI, systolic and mean BP, interventricular septum and relative wall thickness and lower ejection fraction than those without MetS. LVM/h(2.7) was significantly higher in MetS patients (59.14 ± 14.97 vs. 55.33 ± 14.69 g/m(2.7); p = 0.022). Hypertensive patients with MetS had a 2.3-fold higher risk to have LVH/h(2.7) after adjustment for age, SBP and TIS (OR 2.34; 95%CI 1.40-3.92; p = 0.001), but MetS lost its independent relationship with LVH when BMI was included in the model.In Ow/Ob hypertensive patients MetS maintains its role of risk factor for LVH independently of age, SBP, and TIS, resulting in a useful predictor of target organ damage in clinical practice. However, MetS loses its independent relationship when BMI is taken into account, suggesting that the effects on MetS on LV parameters are mainly driven by the degree of adiposity

URBAN LIVEABILITY AS RESULT OF DIFFERENT ASPECTS

Nowadays it is possible to identify a series of parameters that contribute to defining the liveability characteristics of a public space. It is important that all the parameters are satisfied because they are elements that interfere with each other. Morphological characteristics, which partly contribute to defining the environmental performance of the space, together with the functional characteristics of the area, determined by the presence of activities, must be assessed together; however, evaluating them not only in qualitative but also in quantitative terms is not always easy to do. The paper presents a way to evaluate this characteristic of urban space through examples