The remote assessment of parkinsonism supporting ongoing development of interventions in Gaucher disease

Mutations in GBA which are causative of Gaucher disease in their biallelic form, are the most common genetic risk factor for Parkinson's disease (PD). The diagnosis of PD relies upon clinically defined motor features which appear after irreversible neurodegeneration. Prodromal symptoms of PD may provide a means to predict latent pathology, years before the onset of motor features. Previous work has reported prodromal features of PD in GBA mutation carriers, however this has been insufficiently sensitive to identify those that will develop PD. The Remote Assessment of Parkinsonism Supporting Ongoing Development of Interventions in Gaucher Disease (RAPSODI GD) study assesses a large cohort of GBA mutation carriers, to aid development of procedures for earlier diagnosis of PD.

Factores de riesgo genético y diagnóstico prenatal

Objective: To identify genetic risk factors and frequency and to describe congenital defects of the fetus. Methods: The research was conducted at the Genetic Research Institute of the Faculty of Medicine. University of Zulia. Maracaibo. We studied patients who attend to the prenatal genetic clinic. According to the Genetic risk factors Identified, it indicated different prenatal diagnostic procedures: fetal echography, fetal echocardiography, triple maternal serum marker, amniocentesis for fetal karyotype and molecular analysis. Results: We included 568 patients. 79.05% of the total showed only one genetic risk factor and the 20.95% two or more. The advanced maternal age was the most frequent genetic risk factor found (40.85%), followed by first-degree family history with a congenital defect (35.21%), abnormal fetal echography (13.73%), exposure to teratogenic agents (10.39%), history of recurrent abortion (7.04%), history of fetal death (4.22%), consanguinity (1.93%), and history of neonatal death (1.76%). They were diagnosed 101 fetuses with congenital defects, one balanced translocation, two fetal deaths and 26 spontaneous abortions. Conclusion: The genetic risk factors identification, served as a starting point to indicate prenatal diagnostic procedures allowed a health evaluation of the fetus and adequate genetic counseling. Key words: Prenatal diagnosis, Risk factors, Genetic counseling.

Polymorphism of the SLC7A11-PCDH18 locus may be a novel genetic risk factor for juvenile idiopathic arthritis

Полиморфизм T>C rs13128867, расположенный между генами SLC7A11 и PCDH18, первоначально описан как новый локус предрасположенности к болезни Кавасаки (БК) в китайской популяции. Частью нашего исследования по идентификации аллелей риска ювенильных аутоиммунных ревматических заболеваний был анализ связи между полиморфизмом rs13128867 и БК, ювенильным идиопатическим артритом (ЮИА), ювенильной системной красной волчанкой (ЮСКВ) у представителей европеоидной расы, проживающих в Беларуси. В исследование было включено 675 детей и подростков, в том числе 289 пациентов в возрасте до 17 лет на момент начала заболеваний и 386 человек, которые не имели аутоиммунных, воспалительных или суставных заболеваний и служили клиническим контролем. Образцы геномной ДНК были генотипированы методом ПЦР в реальном времени. Сравнение случай-контроль было скорректировано по полу с целью уменьшения неравномерности гендерного распределения между группами, а значения p были скорректированы с использованием метода Бенджамини-Хохберга. Частота минорного аллеля C rs13128867 в контрольной группе составила 17,6%, что соответствует другим европейским популяциям. Результаты анализа ассоциации полиморфизма rs13128867 с БК не совпали с данными, полученными в китайской популяции. Дальнейший анализ выявил ассоциацию минорного аллеля rs13128867 с ЮИА (OR = 1,50; 95% ДИ 1,11-2,03; padj = 0,027) и олигоартритом - наиболее распространенным подтипом ЮИА (OR = 1,67; 95% ДИ 1,17-2,39; padj = 0,016). Также наблюдалась тенденция к ассоциации минорного аллеля rs13128867 с ЮСКВ. Таким образом, результаты исследования впервые продемонстрировали, что полиморфизм rs13128867 SLC7A11-PCHD18 может быть новым генетическим фактором риска ЮИА у пациентов европеоидной расы, однако для подтверждения этого факта необходимы дальнейшие исследования. The rs13128867 (T>C) polymorphism located between SLC7A11 and PCDH18 genes was originally described as a new susceptibility locus for Kawasaki disease (KD) in the Chinese population. Focusing on the identification of risk alleles for juvenile-onset autoimmune rheumatic diseases, the presented paper aims to demonstrate the results of the study undertaken to investigate an association between the rs13128867 polymorphism and KD, juvenile idiopathic arthritis (JIA), and juvenile systemic lupus erythematosus (JSLE) in Caucasians living in Belarus. In total, 675 children and adolescents under 17 at the onset of the disease were included in the study performed, and 386 out of them were without any autoimmune, inflammatory, or joint disorders and served as the clinical control. Genomic DNA samples were genotyped using the real-time PCR technique. Case-control comparison was adjusted for sex with a view of reducing uneven gender distribution between the groups, and p-values were adjusted with the Benjamini-Hochberg procedure. The rs13128867 minor C allele frequency in the control group was found to be 17.6% that is close to other European populations. At the same time, an associative analysis of the rs13128867 polymorphism with KD did not replicate the data known for the Chinese population. Further analysis revealed an association between the rs13128867 minor allele with JIA (OR = 1.50, 95% CI 1.11-2.03, padj = 0.027) and oligoarthritis - the most common JIA subtype (OR = 1.67, 95% CI 1.17-2.39, padj = 0.016). A tendency to association of the rs13128867 minor allele and JSLE was also observed. Thus, the study results demonstrated for the first time that the SLC7A11-PCHD18 rs13128867 polymorphism may be a novel genetic risk factor for JIA in Caucasian patients. However, a further investigation into the rs13128867 polymorphism is strongly required.