Detection of subtelomere imbalance using MLPA: validation, development of an analysis protocol, and application in a diagnostic centre

BACKGROUND: Commercial MLPA kits (MRC-Holland) are available for detecting imbalance at the subtelomere regions of chromosomes; each kit consists of one probe for each subtelomere. METHODS: For validation of the kits, 208 patients were tested, of which 128 were known to be abnormal, corresponding to 8528 genomic regions overall. Validation samples included those with trisomy 13, 18 and 21, microscopically visible terminal deletions and duplications, sex chromosome abnormalities and submicroscopic abnormalities identified by multiprobe FISH. A robust and sensitive analysis system was developed to allow accurate interpretation of single probe results, which is essential as breakpoints may occur between MLPA probes. RESULTS: The validation results showed that MLPA is a highly efficient technique for medium-throughput screening for subtelomere imbalance, with 95% confidence intervals for positive and negative predictive accuracies of 0.951-0.996 and 0.9996-1 respectively. A diagnostic testing strategy was established for subtelomere MLPA and any subsequent follow-up tests that may be required. The efficacy of this approach was demonstrated during 15 months of diagnostic testing when 455 patients were tested and 27 (5.9%) abnormal cases were detected. CONCLUSION: The development of a robust, medium-throughput analysis system for the interpretation of results from subtelomere assays will be of benefit to other Centres wishing to implement such an MLPA-based service

The emerging modern face of mood disorders: a didactic editorial with a detailed presentation of data and definitions

The present work represents a detailed description of our current understanding and knowledge of the epidemiology, etiopathogenesis and clinical manifestations of mood disorders, their comorbidity and overlap, and the effect of variables such as gender and age. This review article is largely based on the 'Mood disorders' chapter of the Wikibooks Textbook of Psychiatry http://en.wikibooks.org/wiki/Textbook_of_Psychiatry/Mood_Disorders

Central sensitization in knee osteoarthritis and fibromyalgia: Beyond depression and anxiety

Objectives: To determine the psychopathological profile of patients with central sensitization (CS) in a sample of knee osteoarthritis, with and without CS, and fibromyalgia, and to compare their psychopathological profiles. Methods: The final sample consists of 19 patients with osteoarthritis and CS (mean 66.37 years ± 8.77), 41 osteoarthritis patients without CS (mean 66.8 ± 7.39 years), 47 fibromyalgia patients (mean 46.47 years ± 7.92) and 26 control subjects (mean 51.56 years ± 11.41). The psychopathological profile was evaluated with the Millon Multiaxial Clinical Inventory. Results: The average score of MCMI-III reflect higher scores in the fibromyalgia and osteoarthritis-CS groups. Patients with osteoarthritis-CS are more likely to report larger scores in Borderline and Major Depression scales. Fibromyalgia patients are more likely to report more increased scores in Somatoform and Major Depression, versus osteoarthritis-CS group. Fibromyalgia patients versus osteoarthritis without CS are more likely to report higher scores in Schizoid, Depression, Histrionic, Sadistic, Borderline, Somatoform, Posttraumatic Stress Disorder and Major Depression scales. Discussion: Patients with CS have less differences in their psychopathological profiles as well as in both osteoarthritis groups and greatest differences are obtained between the fibromyalgia and osteoarthritis without CS, so perhaps presence of CS is the key to differentiate those groups and not chronic pain. An exhaustive assessment brings more accurate psychopathological profiles, thus better psychological treatment could be applied.This work was partially supported by the Ministry of Economy and Competitiveness (Grant PSI2014-53524-P and PSI2017-83777) and the Agency of University and Research Funding Management of the Catalonia Government (Research Groups SGR2017-1198). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome.

Contains fulltext : 88235.pdf (publisher's version ) (Closed access)The clinical use of array comparative genomic hybridization in the evaluation of patients with multiple congenital anomalies and/or mental retardation has recently led to the discovery of a number of novel microdeletion and microduplication syndromes. We present four male patients with overlapping molecularly defined de novo microdeletions of 16q24.3. The clinical features observed in these patients include facial dysmorphisms comprising prominent forehead, large ears, smooth philtrum, pointed chin and wide mouth, variable cognitive impairment, autism spectrum disorder, structural anomalies of the brain, seizures and neonatal thrombocytopenia. Although deletions vary in size, the common region of overlap is only 90 kb and comprises two known genes, Ankyrin Repeat Domain 11 (ANKRD11) (MIM 611192) and Zinc Finger 778 (ZNF778), and is located approximately 10 kb distally to Cadherin 15 (CDH15) (MIM 114019). This region is not found as a copy number variation in controls. We propose that these patients represent a novel and distinctive microdeletion syndrome, characterized by autism spectrum disorder, variable cognitive impairment, facial dysmorphisms and brain abnormalities. We suggest that haploinsufficiency of ANKRD11 and/or ZNF778 contribute to this phenotype and speculate that further investigation of non-deletion patients who have features suggestive of this 16q24.3 microdeletion syndrome might uncover other mutations in one or both of these genes.1 april 201