Mutational Spectrum of the ABCA12 Gene and Genotype-Phenotype Correlation in a Cohort of 64 Patients with Autosomal Recessive Congenital Ichthyosis

Autosomal recessive congenital ichthyosis (ARCI) is a non-syndromic congenital disorder of cornification characterized by abnormal scaling of the skin. The three major phenotypes are lamellar ichthyosis, congenital ichthyosiform erythroderma, and harlequin ichthyosis. ARCI is caused by biallelic mutations in ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, NIPAL4, PNPLA1, SDR9C7, SULT2B1, and TGM1. The most severe form of ARCI, harlequin ichthyosis, is caused by mutations in ABCA12. Mutations in this gene can also lead to congenital ichthyosiform erythroderma or lamellar ichthyosis. We present a large cohort of 64 patients affected with ARCI carrying biallelic mutations in ABCA12. Our study comprises 34 novel mutations in ABCA12, expanding the mutational spectrum of ABCA12-associated ARCI up to 217 mutations. Within these we found the possible mutational hotspots c.4541G>A, p.(Arg1514His) and c.4139A>G, p.(Asn1380Ser). A correlation of the phenotype with the effect of the genetic mutation on protein function is demonstrated. Loss-of-function mutations on both alleles generally result in harlequin ichthyosis, whereas biallelic missense mutations mainly lead to CIE or LI

Sharing brain imaging data in the Open Science era:how and why?

The sharing of human neuroimaging data has great potential to accelerate the development of imaging biomarkers in neurological and psychiatric disorders; however, major obstacles remain in terms of how and why to share data in the Open Science context. In this Health Policy by the European Cluster for Imaging Biomarkers, we outline the current main opportunities and challenges based on the results of an online survey disseminated among senior scientists in the field. Although the scientific community fully recognises the importance of data sharing, technical, legal, and motivational aspects often prevent active adoption. Therefore, we provide practical advice on how to overcome the technical barriers. We also call for a harmonised application of the General Data Protection Regulation across EU countries. Finally, we suggest the development of a system that makes data count by recognising the generation and sharing of data as a highly valuable contribution to the community.</p

Meta-Analysis of Mutations in ALOX12B or ALOXE3 Identified in a Large Cohort of 224 Patients

The autosomal recessive congenital ichthyoses (ARCI) are a nonsyndromic group of cornification disorders that includes lamellar ichthyosis, congenital ichthyosiform erythroderma, and harlequin ichthyosis. To date mutations in ten genes have been identified to cause ARCI: TGM1, ALOX12B, ALOXE3, NIPAL4, CYP4F22, ABCA12, PNPLA1, CERS3, SDR9C7, and SULT2B1. The main focus of this report is the mutational spectrum of the genes ALOX12B and ALOXE3, which encode the epidermal lipoxygenases arachidonate 12-lipoxygenase, i.e., 12R type (12R-LOX), and the epidermis-type lipoxygenase-3 (eLOX3), respectively. Deficiency of 12R-LOX and eLOX3 disrupts the epidermal barrier function and leads to an abnormal epidermal differentiation. The type and the position of the mutations may influence the ARCI phenotype; most patients present with a mild erythrodermic ichthyosis, and only few individuals show severe erythroderma. To date, 88 pathogenic mutations in ALOX12B and 27 pathogenic mutations in ALOXE3 have been reported in the literature. Here, we presented a large cohort of 224 genetically characterized ARCI patients who carried mutations in these genes. We added 74 novel mutations in ALOX12B and 25 novel mutations in ALOXE3. We investigated the spectrum of mutations in ALOX12B and ALOXE3 in our cohort and additionally in the published mutations, the distribution of these mutations within the gene and gene domains, and potential hotspots and recurrent mutations

Imaging executive functions in Parkinson's disease: An activation likelihood estimation meta-analysis

INTRODUCTION:Executive dysfunction is a common and early cognitive symptom in Parkinson's disease (PD) with a detrimental effect on quality of life of patients and their care givers. Thus, a number of neuroimaging studies investigated the underlying neural correlates of such an impairment. Results of individual studies, however, are not univocal in terms of location and directionality of associated functional brain changes.OBJECTIVE:To assess convergence of abnormal brain activation in patients with PD during the performance of tasks probing executive functions (EF).METHODS:We screened the functional imaging literature on EF in PD using the PubMed database, extracted reported stereotactic data and tested for convergence of deviant neural activation in patients with PD when compared to healthy controls (HC) using a coordinate-based activation likelihood estimation approach.RESULTS:We identified 22 eligible papers from which the main proportion was targeted at the investigation of working memory encompassing 354 patients and 306 HC. Surprisingly, no significant converging aberrant activation between HC and patients (ON, OFF or ON + OFF medication, respectively) could be observed when controlling for multiple comparisons using family-wise error correction on cluster-level.CONCLUSION:We conclude that there is currently not enough available evidence to pinpoint a specific neural correlate associated with executive dysfunction in PD. This might be due to the small number of studies performed and their methodical inconsistency. Therefore, it is important to conduct more research regarding functional brain changes associated with EF in these patients using more consistent frameworks and bigger samples

PET and SPECT Imaging of Neurodegenerative Diseases

Today, a number of complementary molecular imaging methods are at our disposal, which can make a relevant contribution to early diagnosis, differential diagnosis, disease monitoring, and follow-up of neurodegenerative diseases. This includes long-established FDG-PET which provides valuable information on location and extent of pathology and has demonstrated great value for early diagnosis, short-term prognosis, and for differential diagnosis of various disorders on the basis of the endophenotype of disease. Imaging of the dopaminergic system has proven value in the workup of movement disorders. More recently introduced, amyloid-PET for the first time allows in vivo diagnostic assessment of a molecular neuropathology, most valuable for verification or exclusion of Alzheimer disease (AD), independent of the symptomatic appearance. Finally, new tracers for tau-PET imaging may allow the assessment of location, extent, and specific type of pathology, which may hold great value for early and differential diagnosis of neurodegeneration in the future