CREB-binding protein and p300 function as transcriptional coactivators in the regulation of gene expression through various signal-transduction pathways. Both are potent histone acetyl transferases. A certain level of CREB-binding protein is essential for normal development, since inactivation of one allele causes Rubinstein-Taybi syndrome (RSTS). There is a direct link between loss of acetyl transferase activity and RSTS, which indicates that the disorder is caused by aberrant chromatin regulation. We screened the entire CREB-binding protein gene (CBP) for mutations in patients with RSTS by using methods that find point mutations and larger rearrangements. In 92 patients, we were able to identify a total of 36 mutations in CBP. By using multiple ligation-dependent probe amplification, we found not only several deletions but also the first reported intragenic duplication in a patient with RSTS. We extended the search for mutations to the EP300 gene and showed that mutations in EP300 also cause this disorder. These are the first mutations identified in EP300 for a congenital disorder.

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Part of the clinical variability in RSTS is explained by genetic heterogeneity. The diagnosis of RSTS must be expanded to include patients without broad thumbs or halluces.

OBJECTIVE -Gastric bypass and biliopancreatic diversion (BPD) are known to have a beneficial effect on glucose metabolism superior to that of the other bariatric operations. Thanks to its excellent weight loss results and to its specific actions, BPD has proven able to guarantee permanent normalization of serum glucose, triglygeride, and cholesterol levels in the vast majority, if not the totality, of operated patients. However, clinical studies on the duration of these effects in large patient populations are still lacking.RESEARCH DESIGN AND METHODS -The files of 312 BPD obese patients with type 2 diabetes operated on from June 1984 to January 1993 were examined. Pre-and postoperative serum glucose, triglyceride, and cholesterol levels, along with arterial pressure measurements, were considered.RESULTS -After BPD, fasting serum glucose concentration fell within normal values in all but two of the operated subjects and remained in the physiological range in all but six up until 10 years. Serum triglyceride and total cholesterol steadily normalized in all subjects with abnormally high preoperative values, and arterial hypertension disappeared in the vast majority of the preoperatively hypertensive patients.CONCLUSIONS -BPD proved able to reverse all the major components of the metabolic syndrome in nearly all the operated subjects, with results being strictly maintained over a 10-year follow-up period. This outcome, which far exceeds those following similar weight loss at short or long term obtained by any other means, confirms the existence of specific actions of BPD on the major components of metabolic syndrome. Diabetes Care 28:2406 -2411, 2005O besity is a serious health problem associated with important morbidity and mortality (1,2), much of which is secondary to conditions either determined or exacerbated by the obesity itself. These conditions, which include type 2 diabetes, arterial hypertension, and hyperlipidemia (3-7), are major causes of cardiovascular disease, as well as retinopathy, neuropathy, and renal disease. The prevalence of type 2 diabetes among severely obese patients is high, and despite medical treatment, type 2 diabetes is a leading cause of an overall increased mortality in obesity.Previous reports have shown that diabetic obese patients become euglycemic following surgery for severe obesity (8 -10). Roux-en-Y gastric bypass and biliopancreatic diversion (BPD) are the most effective surgical procedures for the treatment of type 2 diabetes in obese patients, both being followed by normalization of plasma glucose and insulin concentrations in the vast majority of the operated individuals (8,(11)(12)(13)(14). Plasma insulin and glucose concentration often fall back into a normal range after resumption of food intake and long before a significant weight loss occurs, thus suggesting that the control of diabetes might be a specific effect of the operation that contributes with the weight loss to the amelioration of the metabolic status (9,15,16). Although the marked immediate and sustained im...

Dietary treatment is the cornerstone of therapy for phenylketonuria (PKU), but adherence to low- phenylalanine diet progressively decreases after adolescence. We designed a survey to characterize the dietary habits of Italian adult PKU patients and to identify psychological factors influencing disease perception and adherence to diet. Participants to the survey (n = 111; response rate 94%) were asked to complete a structured questionnaire. Patients appeared to have an altered perception and awareness of the disease. About 40% of them did not consider PKU a disease and, despite declaring regular monitoring of phenylalanine levels (85%), nearly half of them reported a high plasma value over the last 6 months (>600 μmol/L, 48%) or were unable to specify it (31%). Adherence to PKU diet was unsatisfactory, with increased consumption of natural protein sources and reduced daily use of amino-acid supplements (<4–5 times/day in 82% patients). In addition to the intrinsic characteristics of AA formula (palatability, ease of use), the most important factor influencing their consumption was the increased social pressure associated with their use (55%). Plasma phenylalanine periodical measurements (61%) and examinations at metabolic centers (49%) were considered relevant for compliance to diet. In Italian adult PKU patients dietary management was found to be inadequate, likely due to inappropriate perception and knowledge of the disease, and lack of awareness of the negative impact of poor metabolic control in adult life. Clinicians should consider implementing more intense and tailored educational measures, as well as structured transitional care processes.