Casa Sollievo della Sofferenza

About: Casa Sollievo della Sofferenza is a healthcare organization based out in San Giovanni Rotondo, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 2234 authors who have published 6183 publications receiving 239811 citations. The organization is also known as: Home for Relief of the Suffering.

Two high throughput technologies to detect segmental aneuploidies identify new Williams-Beuren syndrome patients with atypical deletions

Abstract: OBJECTIVE: To develop and compare two new technologies for diagnosing a contiguous gene syndrome, the Williams-Beuren syndrome (WBS). METHODS: The first proposed method, named paralogous sequence quantification (PSQ), is based on the use of paralogous sequences located on different chromosomes and quantification of specific mismatches present at these loci using pyrosequencing technology. The second exploits quantitative real time polymerase chain reaction (QPCR) to assess the relative quantity of an analysed locus. RESULTS: A correct and unambiguous diagnosis was obtained for 100% of the analysed samples with either technique (n = 165 and n = 155, respectively). These methods allowed the identification of two patients with atypical deletions in a cohort of 182 WBS patients. Both patients presented with mild facial anomalies, mild mental retardation with impaired visuospatial cognition, supravalvar aortic stenosis, and normal growth indices. These observations are consistent with the involvement of GTF2IRD1 or GTF2I in some of the WBS facial features. CONCLUSIONS: Both PSQ and QPCR are robust, easy to interpret, and simple to set up. They represent a competitive alternative for the diagnosis of segmental aneuploidies in clinical laboratories. They have advantages over fluorescence in situ hybridisation or microsatellites/SNP genotyping for detecting short segmental aneuploidies as the former is costly and labour intensive while the latter depends on the informativeness of the polymorphisms.

(TA)8 allele in the UGT1A1 gene promoter of a Caucasian with Gilbert's syndrome.

Abstract: BACKGROUND AND OBJECTIVE: Gilbert's syndrome, a chronic non-hemolytic unconjugated hyperbilirubinemia, is caused by a reduction in the activity of hepatic bilirubin UDP-glucuronosyltransferase (UGT1A1). This reduction has been shown to be due to a polymorphism in the promoter region of the UGT1A1 gene. The presence of seven thymine adenine (TA) repeats reduces the efficiency of transcription of the UGT1A1 gene. To elucidate the genetic background of a patient affected by Gilbert's syndrome, we collected blood samples from family members for the analysis of the A(TA)nTAA motif in the promoter region of the UGT1A1 gene. DESIGN AND METHODS: Analysis of the A(TA)nTAA motif in the promoter region of the UGT1A1 gene was performed by PCR. Estimation of UGT1A1 promoter containing the variable (TA) repeats was performed by using a luciferase reporter system. RESULTS: Three different genotypes were identified due to the presence of (TA)6, (TA)7 and (TA)8 repeats. The production of luciferase decreases in inverse relation to the number of repeats. INTERPRETATION AND CONCLUSIONS: The (TA)7 polymorphism, associated with Gilbert syndrome, is the only allele found up to now in white populations, while two other variants (TA)5 and (TA)8 have been identified in black populations. We describe here the first case of a subject affected by Gilbert's syndrome who is heterozygous for the (TA)8 allele in the promoter region of the UGT1A1 gene. This polymorphism, as well as the (TA)7 one, is associated with an increased level of bilirubin and a significant reduction of transcription activity of the UGT1A1 gene.

Serum resistin, cardiovascular disease and all-cause mortality in patients with type 2 diabetes.

Abstract: BACKGROUND High serum resistin has been associated with increased risk of cardiovascular disease in the general population, Only sparse and conflicting results, limited to Asian individuals, have been reported, so far, in type 2 diabetes. We studied the role of serum resistin on coronary artery disease, major cardiovascular events and all-cause mortality in type 2 diabetes. METHODS We tested the association of circulating resistin concentrations with coronary artery disease, major cardiovascular events (cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) and all-cause mortality in 2,313 diabetic patients of European ancestry from two cross-sectional and two prospective studies. In addition, the expression of resistin gene (RETN) was measured in blood cells of 68 diabetic patients and correlated with their serum resistin levels. RESULTS In a model comprising age, sex, smoking habits, BMI, HbA1c, and insulin, antihypertensive and antidyslipidemic therapies, serum resistin was associated with coronary artery disease in both cross-sectional studies: OR (95%CI) per SD increment = 1.35 (1.10-1.64) and 1.99 (1.55-2.55). Additionally, serum resistin predicted incident major cardiovascular events (HR per SD increment = 1.31; 1.10-1.56) and all-cause mortality (HR per SD increment = 1.16; 1.06-1.26). Adjusting also for fibrinogen levels affected the association with coronary artery disease and incident cardiovascular events, but not that with all cause-mortality. Finally, serum resistin was positively correlated with RETN mRNA expression (rho = 0.343). CONCLUSIONS This is the first study showing that high serum resistin (a likely consequence, at least partly, of increased RETN expression) is a risk factor for cardiovascular disease and all-cause mortality in diabetic patients of European ancestry.

TERT Promoter Mutations in Papillary Thyroid Microcarcinomas

Abstract: Background: Small papillary thyroid carcinomas have contributed to the worldwide increased incidence of differentiated thyroid cancer observed over the past decades. However, the mortality rate has not changed over the same period of time, raising questions about the possibility that thyroid cancer patients, especially those with small tumors, are overdiagnosed and overtreated. Molecular prognostic marker able to discriminate aggressive thyroid cancers from those with an indolent course would be of great relevance to tailor the therapeutic approach and reduce overtreatment. Mutations in the TERT promoter were recently reported to correlate strongly with aggressiveness in advanced forms of thyroid cancer, holding promise for a possible clinical application. The occurrence and potential clinical relevance of TERT mutations in papillary thyroid microcarcinomas (mPTCs) is currently unknown. This study aimed to analyze the occurrence of two TERT promoter mutations (-124C>T and -146C>T) and their potential asso...