A novel point mutation within the EDA gene causes an exon dropping in mature RNA in Holstein Friesian cattle breed affected by X-linked anhidrotic ectodermal dysplasia

<p>Abstract</p> <p>Background</p> <p>X-linked anhidrotic ectodermal dysplasia is a disorder characterized by abnormal development of tissues and organs of ectodermal origin caused by mutations in the <it>EDA </it>gene. The bovine <it>EDA </it>gene encodes the ectodysplasin A, a membrane protein expressed in keratinocytes, hair follicles and sweat glands, which is involved in the interactions between cell and cell and/or cell and matrix. Four mutations causing ectodermal dysplasia in cattle have been described so far.</p> <p>Results</p> <p>We identified a new single nucleotide polymorphism (SNP) at the 9^thbase of exon 8 in the <it>EDA </it>gene in two calves of Holstein Friesian cattle breed affected by ectodermal dysplasia. This SNP is located in the exonic splicing enhancer (ESEs) recognized by SRp40 protein. As a consequence, the spliceosome machinery is no longer able to recognize the sequence as exonic and causes exon skipping. The mutation determines the deletion of the entire exon (131 bp) in the RNA processing, causing a severe alteration of the protein structure and thus the disease.</p> <p>Conclusion</p> <p>We identified a mutation, never described before, that changes the regulation of alternative splicing in the <it>EDA </it>gene and causes ectodermal dysplasia in cattle. The analysis of the SNP allows the identification of carriers that can transmit the disease to the offspring. This mutation can thus be exploited for a rational and efficient selection of unequivocally healthy cows for breeding.</p

Genetic variation and relationships among Turkish water buffalo populations

The genetic variation and relationships among six Turkish water buffalo populations,typical of different regions was assessed using a set of twenty-six heterologous (bovine) microsatellite markers. Between 7 and 17 different alleles were identified per microsatellite in a total of 254 alleles. The average number of alleles across all loci in all the analyzed populations was found to be 12.57. The expected mean heterozygosity (HE) per population was between 0.5 and 0.58. Significant departures from Hardy-Weinberg equilibrium were observed for 44 locus-population combinations. Population differentiation was analyzed by estimation of the FST index (values ranging from 0.053 to 0.123) among populations. In the PCA analysis the Merzifon population showed the highest differentiation compared to the others. Also some individuals of the Danamandira population appeared clearly separated. Instead Afyon, Coskun, Pazar and Thural populations represented one single cluster. The assignment of individuals to their source populations, performed using the Bayesian clustering approach implemented in STRUCTURE 2.2 software, has evidenced a high differentiation of Merzifon and Danamandira populations as well. The results of this study could be useful for the development of conservation strategies of the Turkish buffalo

Pulmonary arterial hypertension and interstitial lung fibrosis in systemic sclerosis: One-stop shop assessment with cardiac and chest ultrasound

Background: Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are common complications of systemic sclerosis (SSc). Echocardiography evaluates PAH, and chest sonography detects even mild ILC as ultrasound lung comets (ULC), i.e. multiple comet-tails fanning out from the lung surface and originating from subpleural interlobular septa thickened by fibrosis. Aim: to assess ILD and PAH by integrated cardiac and chest ultrasound in SSc. Materials and methods: We enrolled 30 consecutive SSc patients (age=54?13 years, 23 females) in the Rheumatology Clinic of Pisa University. In all, we assessed Systolic Pulmonary Arterial Pressure (SPAP), from maximal velocity of tricuspid regurgitation flow, and ULC score with chest sonography (summing the number of ULC from each scanning space of anterior and posterior right and left chest, from second to fifth intercostal space). All patients underwent plasma assay for anti-topoisomerase antibodies (anti-Scl70), associated with development of pulmonary fibrosis. Twenty-eight patients also underwent High Resolution Computed Tomography, HRCT (from 0=no fibrosis to 3=honey combing). Results: ULC number - but not SPAP - was correlated to HRCT fibrosis and presence SSc-70 antibodies (see figure). ULC number was similar in localized or diffuse forms (16?20 vs. 21?19, p=ns) and was unrelated to SPAP (r=0.216, p=ns). Conclusions: Cardiac and chest sonography assessment of SPAP and ULC allow a complete, simple, radiation-free characterization of vascular and interstitial lung involvement in SSc - all in one setting and with the same instrument, same transducer and the same sonographer. In particular, ULC number, but not SPAP, is associated with HRCT evidence of lung fibrosis and presence of Scl-70 antibodies

Ultrasound lung comets in systemic sclerosis: a chest sonography hallmark of pulmonary interstitial fibrosis

Objective. To assess the correlation between ultrasound lung comets (ULCs, a recently described echographic sign of interstitial lung fibrosis) and the current undisputed gold-standard high-resolution CT (HRCT) to detect pulmonary fibrosis in patients with SSc. Methods. We enrolled 33 consecutive SSc patients (mean age 5413 years, 30 females) in the Rheumatology Clinic of the University of Pisa. We assessed ULCs and chest HRCT within 1 week independently in all the patients. ULC score was obtained by summing the number of lung comets on the anterior and posterior chest. Pulmonary fibrosis was quantified by HRCT with a previously described 30-point Warrick score. Results. Presence of ULCs (defined as a total number more than 10) was observed in 17 (51%) SSc patients. Mean ULC score was 3750, higher in the diffuse than in the limited form (7366 vs 2135; P<0.05). A significant positive linear correlation was found between ULCs and Warrick scores (r?0.72; P<0.001). Conclusions. ULCs are often found in SSc, are more frequent in the diffuse than the limited form and are reasonably well correlated with HRCT-derived assessment of lung fibrosis. They represent a simple, bedside, radiation-free hallmark of pulmonary fibrosis of potential diagnostic and prognostic value

Lung Ultrasound for the Evaluation of Pulmonary Congestion in Outpatients

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Left atrial dysfunction detected by speckle tracking in patients with systemic sclerosis

BACKGROUND: Cardiac involvement is a relevant clinical finding in systemic sclerosis (SSc) and is associated with poor prognosis. Left atrial (LA) remodeling and/or dysfunction can be an early sign of diastolic dysfunction. Two-dimensional speckle tracking echocardiography (STE) is a novel and promising tool for detecting very early changes in LA myocardial performance. AIM: To assess whether STE strain parameters may detect early alterations in LA function in SSc patients. METHODS: Forty-two SSc patients (Group 1, age 50 +/- 14 years, 95% females) without clinical evidence for cardiac involvement and 42 age- and gender-matched control subjects (Group 2, age 49 +/- 13 years, 95% females) were evaluated with comprehensive 2D and Doppler echocardiography, including tissue Doppler imaging analysis. Positive peak left atrial longitudinal strain ( pos peak), second positive left atrial longitudinal strain (sec pos peak), and negative left atrial longitudinal strain ( neg peak) were measured using a 12-segment model for the LA, by commercially available semi-automated 2D speckle-tracking software (EchoPac PC version 108.1.4, GE Healthcare, Horten, Norway). RESULTS: All SSc patients had a normal left ventricular ejection fraction (63.1 +/- 4%). SSc patients did not differ from controls in E/A (Group 1 = 1.1 +/- 0.4 vs Group 2 = 1.3 +/- 0.4, p = .14) or pulmonary arterial systolic pressure (Group 1 = 24.1 +/- 8 mmHg vs Group 2 = 21 +/- 7 mmHg, p = .17). SSc patients did not show significantly different indexed LA volumes (Group 1 = 24.9 +/- 5.3 ml/m2 vs Group 2 = 24.7 +/- 4.4 ml/m2, p = .8), whereas E/e' ratio was significantly higher in SSc (Group 1 = 7.6 +/- 2.4 vs Group 2 = 6.5 +/- 1.7, p<0.05), although still within normal values. LA strain values were significantly different between the two groups ( pos peak Group 1 = 31.3 +/- 4.2% vs Group 2 = 35.0 +/- 7.6%, p < .01, sec pos peak Group 1 = 18.4 +/- 4 vs Group 2 = 21.4 +/- 7.6, p < 0.05). CONCLUSION: 2D speckle-tracking echocardiography is a sensitive tool to assess impairment of LA mechanics, which is detectable in absence of changes in LA size and volume, and may represent an early sign of cardiac involvement in patients with SSc

Stress echo 2020 : the international stress echo study in ischemic and non-ischemic heart disease

Background: Stress echocardiography (SE) has an established role in evidence-based guidelines, but recently its breadth and variety of applications have extended well beyond coronary artery disease (CAD). We lack a prospective research study of SE applications, in and beyond CAD, also considering a variety of signs in addition to regional wall motion abnormalities. Methods: In a prospective, multicenter, international, observational study design, > 100 certified high-volume SE labs (initially from Italy, Brazil, Hungary, and Serbia) will be networked with an organized system of clinical, laboratory and imaging data collection at the time of physical or pharmacological SE, with structured follow-up information. The study is endorsed by the Italian Society of Cardiovascular Echography and organized in 10 subprojects focusing on: contractile reserve for prediction of cardiac resynchronization or medical therapy response; stress B-lines in heart failure; hypertrophic cardiomyopathy; heart failure with preserved ejection fraction; mitral regurgitation after either transcatheter or surgical aortic valve replacement; outdoor SE in extreme physiology; right ventricular contractile reserve in repaired Tetralogy of Fallot; suspected or initial pulmonary arterial hypertension; coronary flow velocity, left ventricular elastance reserve and B-lines in known or suspected CAD; identification of subclinical familial disease in genotype-positive, phenotype- negative healthy relatives of inherited disease (such as hypertrophic cardiomyopathy). Results: We expect to recruit about 10,000 patients over a 5-year period (2016-2020), with sample sizes ranging from 5,000 for coronary flow velocity/ left ventricular elastance/ B-lines in CAD to around 250 for hypertrophic cardiomyopathy or repaired Tetralogy of Fallot. This data-base will allow to investigate technical questions such as feasibility and reproducibility of various SE parameters and to assess their prognostic value in different clinical scenarios. Conclusions: The study will create the cultural, informatic and scientific infrastructure connecting high-volume, accredited SE labs, sharing common criteria of indication, execution, reporting and image storage of SE to obtain original safety, feasibility, and outcome data in evidence-poor diagnostic fields, also outside the established core application of SE in CAD based on regional wall motion abnormalities. The study will standardize procedures, validate emerging signs, and integrate the new information with established knowledge, helping to build a next-generation SE lab without inner walls