Contact allergy to methylchloroisothiazolinone/methylisothiazolinone in north-eastern Italy: a temporal trend from 1996 to 2016

BACKGROUND: Methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) (Kathon\uae CG) is a common preservative used in industrial products, owing to its strong biocide effect. Contact allergy to MCI/MI has been reported in different occupations, including mechanics, hairdressers and healthcare workers. OBJECTIVE: To retrospectively analyse the temporal trend of MCI/MI sensitization in north-eastern Italy and to evaluate the associations with occupations in our geographical area. METHODS: From 1996 to 2016, 27 381 patients with suspected allergic contact dermatitis were patch tested in eight departments of Dermatology or Occupational Medicine in north-eastern Italy. Individual characteristics were collected through a standardized questionnaire. RESULTS: The overall prevalence of MCI/MI sensitization was 4.2%, with the highest prevalence found in women and in patients younger than 25 years. MCI/MI sensitization was significantly associated with atopic eczema (OR: 1.34, 95% CI: 1.10-1.70), hand/forearm dermatitis (OR: 1.20, 95% CI: 1.05-1.36) and face dermatitis (OR 1.30, 95% CI: 1.10-1.40). There was a significant association between MCI/MI sensitization and chemical processing workers (OR 1.74, 95% CI: 1.03-2.94), while mechanics and healthcare workers resulted more sensitized to this hapten only in the last 3 years. CONCLUSIONS Sensitization to MCI/MI is rising in the last years in Triveneto region, the 'epidemic' of sensitization to MCI/MI is mainly driven by extra-occupational dermatitis, and sensitization in some occupational groups is emerging only in the last years. A full labelling is compulsory for all products that contain isothiazolinones, to permit to identify the culprit agent

Germline and somatic mutations in cortical malformations: Molecular defects in Argentinean patients with neuronal migration disorders

<div><p>Neuronal migration disorders are a clinically and genetically heterogeneous group of malformations of cortical development, frequently responsible for severe disability. Despite the increasing knowledge of the molecular mechanisms underlying this group of diseases, their genetic diagnosis remains unattainable in a high proportion of cases. Here, we present the results of 38 patients with lissencephaly, periventricular heterotopia and subcortical band heterotopia from Argentina. We performed Sanger and Next Generation Sequencing (NGS) of <i>DCX</i>, <i>FLNA</i> and <i>ARX</i> and searched for copy number variations by MLPA in <i>PAFAH1B1</i>, <i>DCX</i>, <i>POMT1</i>, and <i>POMGNT1</i>. Additionally, somatic mosaicism at 5% or higher was investigated by means of targeted high coverage NGS of <i>DCX</i>, <i>ARX</i>, and <i>PAFAH1B1</i>. Our approach had a diagnostic yield of 36%. Pathogenic or likely pathogenic variants were identified in 14 patients, including 10 germline (five novel) and 4 somatic mutations in <i>FLNA</i>, <i>DCX</i>, <i>ARX</i> and <i>PAFAH1B1</i> genes. This study represents the largest series of patients comprehensively characterized in our population. Our findings reinforce the importance of somatic mutations in the pathophysiology and diagnosis of neuronal migration disorders and contribute to expand their phenotype-genotype correlations.</p></div

Whole exome sequencing in neurogenetic odysseys: An effective, cost- and time-saving diagnostic approach.

Diagnostic trajectories for neurogenetic disorders frequently require the use of considerable time and resources, exposing patients and families to so-called "diagnostic odysseys". Previous studies have provided strong evidence for increased diagnostic and clinical utility of whole-exome sequencing in medical genetics. However, specific reports assessing its utility in a setting such as ours- a neurogeneticist led academic group serving in a low-income country-are rare.To assess the diagnostic yield of WES in patients suspected of having a neurogenetic condition and explore the cost-effectiveness of its implementation in a research group located in an Argentinean public hospital.This is a prospective study of the clinical utility of WES in a series of 40 consecutive patients selected from a Neurogenetic Clinic of a tertiary Hospital in Argentina. We evaluated patients retrospectively for previous diagnostic trajectories. Diagnostic yield, clinical impact on management and economic diagnostic burden were evaluated.We demonstrated the clinical utility of Whole Exome Sequencing in our patient cohort, obtaining a diagnostic yield of 40% (95% CI, 24.8%-55.2%) among a diverse group of neurological disorders. The average age at the time of WES was 23 (range 3-70). The mean time elapsed from symptom onset to WES was 11 years (range 3-42). The mean cost of the diagnostic workup prior to WES was USD 1646 (USD 1439 to 1853), which is 60% higher than WES cost in our center.WES for neurogenetics proved to be an effective, cost- and time-saving approach for the molecular diagnosis of this heterogeneous and complex group of patients