Case Report of a Juvenile Patient with Autism Spectrum Disorder with a Novel Combination of Copy Number Variants in ADGRL3 (LPHN3) and Two Pseudogenes.

We report the finding of two copy number variants (CNVs) in a 12-year-old boy presenting both with autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Clinical features included aggressive behavior, mood instability, suicidal statements, repetitive and restrictive behavior, sensitivity to noise, learning problems and dyslexia, though no intellectual disability was present. Using array-based comparative genomic hybridization (array-CGH), we identified two CNVs, both triplex duplications of 324 kb on 3p26.3, and 284 kb on 4q13.1, respectively. One of the CNVs is located on chromosome 4q13.1 in the region of the gene encoding for adhesion G protein-coupled receptor L3 (ADGRL3, former name: latrophilin-3, LPHN3), the other on chromosome 3p26.3 in the region of the two pseudogenes AC090043.1 and RPL23AP39. The patient described in the present study showed increased symptoms under methylphenidate treatment but responded positively to 3 mg per day of the atypical neuroleptic drug aripiprazole. To our knowledge, this is the first report of a CNV in the ADGRL3 gene and its first association with ASD in humans.

The influence of storage temperature during machine perfusion on preservation quality of marginal donor livers.

BACKGROUND: Although non-heart-beating donors have the potential to increase the number of available organs, the livers are used very seldom because of the risk of primary non-function. There is evidence that machine perfusion is able to improve the preservation of marginal organs, and therefore we evaluated in our study the influence of the perfusate temperature during oxygenated machine perfusion on the graft quality. METHODS: Livers from male Wistar rats were harvested after 60-min warm ischemia induced by cardiac arrest. The portal vein was cannulated and the liver flushed with Lifor (Lifeblood Medical, Inc.) organ preservation solution for oxygenated machine perfusion (MP) at 4, 12 or 21 degrees C. Other livers were flushed with HTK and stored at 4 degrees C by conventional cold storage (4 degrees C-CS). Furthermore two groups with either warm ischemic damage only or without any ischemic damage serve as control groups. After 6h of either machine perfusion or cold storage all livers were normothermic reperfused with Krebs-Henseleit buffer, and functional as well as structural data were analyzed. RESULTS: Contrary to livers stored by static cold storage, machine perfused livers showed independently of the perfusate temperature a significantly decreased enzyme release of hepatic transaminases (ALT) during isolated reperfusion. Increasing the machine perfusion temperature to 21 degrees C resulted in a marked reduction of portal venous resistance and an increased bile production. CONCLUSIONS: Oxygenated machine perfusion improves viability of livers after prolonged warm ischemic damage. Elevated perfusion temperature of 21 degrees C reconstitutes the hepatic functional capacity better than perfusion at 4 or 12 degrees C.