Targeted next generation sequencing approach identifies nineteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann Syndrome, Molecular and Cellular Endocrinology (2016), doi: 10.1016/ j.mce.2016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
AbstractThe genetic basis is unknown for ~60% of normosmic hypogonadotropic hypogonadism (nHH)/Kallmann syndrome (KS). DNAs from (17 male and 31 female) nHH/KS patients were analyzed by targeted next generation sequencing (NGS) of 261 genes involved in hypothalamic, pituitary, and/or olfactory pathways, or suggested by chromosome rearrangements. Selected variants were subjected to Sanger DNA sequencing, the gold standard. The frequency of Sanger-confirmed variants was determined using the ExAC database. Variants were classified as likely pathogenic (frameshift, nonsense, and splice site) or predicted pathogenic (nonsynonymous missense). Two novel FGFR1 mutations were identified, as were 19 new candidate genes including:
The incidence of cholecystectomy in children has increased considerably since the early 1990s.Management of gallbladder disease in children must include an awareness of choledocholithiasis treatment strategies. Both endoscopic retrograde cholangiopancreatography (ERCP) and common bile duct exploration (open or laparoscopic) are accepted management techniques for choledocholithiasis. Laparoscopic cholecystectomy with preoperative or postoperative ERCP is at least a two-procedure process while cholecystectomy with laparoscopic common bile duct exploration (LCBDE) can provide definitive treatment in a single procedure under one anesthetic. Despite this, the trend over the last decade continues towards less LCBDE utilization in favor of ERCP. This trend has resulted in decreased familiarity with LCBDE by adult and pediatric surgeons and their trainees. Access to the necessary tools and education on the technical aspects can allow for successful single-stage treatment of choledocholithiasis by surgeons during laparoscopic cholecystectomy. This may include a pre-defined stepwise algorithm and understanding of all the equipment and resources necessary to perform a LCBDE. Ultimately, increased understanding of the equipment and procedural steps necessary for LCBDE will result in widened adoption of the technique and thus confer advantages to the patient such as decreased length of stay and fewer required anesthetics.
Laparoscopic cholecystectomy (LC) with laparoscopic common bile duct exploration (LCBDE) is gaining traction for the management of choledocholithiasis. Liver function tests (LFTs) are often used to determine the success of ductal clearance, yet the impact of differing therapeutic interventions, endoscopic retrograde cholangiopancreatography (ERCP) or LCBDE, have on postprocedure LFT is insufficiently described. We hypothesize that these interventions have different postoperative LFT profiles. The preprocedural and postprocedural total bilirubin (Tbili), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were analyzed of 167 patients who had successful ERCPs (117) or LCBDEs (50). Endoscopic retrograde cholangiopancreatography patients demonstrated a significant decrease in all LFTs postprocedure (n = 117; P = <0.001 for all) with a continued downtrend when a second set of LFTs was obtained (n = 102; P = <0.001 for all). For successful LC+LCBDEs, there was no significant change between preoperative and 1st postoperative Tbili, AST, ALT, and ALP and the 2nd postoperative labs.
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