Estudio clínico genético en pacientes con complejo de esclerosis tuberosa

Introduction: Tuberous sclerosis complex (TSC) is a multisystem autosomal dominant disease caused by mutations in the tumor suppressor genes TSC1 or TSC2. Objective: To characterize clinically and genetically patients diagnosed with TSC. Patients and method: Descriptive study of clinical records from a pediatric neuropsychiatry department of 42 patients diagnosed with TSC and genetic study of 21 of them. The exon 15 of the TSC1 gene and exons 33, 36 and 37 of the TSC2 gene were amplified by polymerase chain reaction and sequenced. The relationship between the mutations found with the severity and clinical evolution were analyzed. Results: In 61.9% of the patients the symptoms began before 6 months of age. The most frequent initial manifestations of TSC were new onset of seizures (73.8%) and the detection of cardiac rhabdomyomas (16.6%). During the evolution of the disease all patients had neurological involvement; 92.9% had epilepsy. All patients presented hypomelanotic spots, 47.6% facial angiofibromas, 23.8% Shagreen patch, 47.6 heart rhabdomyomas and 35.7% retinal hamartomas. In the genetic study of 21 patients, two heterozygous pathogenic mutations in TSC1 and one in TSC2 genes were identified. The latter had a more severe clinical phenotype. Conclusions: Neurological and dermatological were the most frequent manifestations in patients with TSC. Two pathogenic mutations in TSC1 and one in TSC2 genes were identified. The patient with TSC2 mutation manifested a more severe clinical phenotype.Seed Project of the Chilean Society of Pediatrics (Proyecto Semilla de la Sociedad Chilena de Pediatría)

MUC1/SEC and MUC1/Y overexpression is associated with inflammation in Sjogren's syndrome

Artículo de publicación ISIOBJECTIVES: To evaluate the expression and localization of MUC1/SEC and MUC1/Y isoforms in labial salivary glands (LSG) from Sj€ogren’s syndrome patients (SS patients), as well as their in vitro expression induced by cytokines. SUBJECTS AND METHODS: Labial salivary gland from 27 primary SS patients and 22 non-SS sicca subjects were studied. Relative MUC1/SEC and MUC1/Y mRNA levels were determined by qPCR and protein levels by Western blotting. Induction of mucin mRNAs was assayed in vitro. Immunohistochemistry was used for localization. RESULTS: Relative MUC1/SEC and MUC1/Y mRNA and protein levels were significantly higher in LSG from SS patients. These mRNAs were induced by cytokines. MUC1/SEC and MUC1/Y were detected in acini apical region of control LSGs, and significant cytoplasmic accumulation was observed in acini of SS patients. MUC1/Y localized in acinar nuclei and cytoplasm of inflammatory cells of LSG from SS patients. A strong positive correlation was observed between cellular MUC1/SEC levels and glandular function determined by scintigraphy. CONCLUSIONS: We show for the first time that MUC1/SEC and MUC1/Y are expressed in LSG of both SS patients and non-SS sicca subjects. The observed overexpression and aberrant localization of MUC1/SEC and MUC1/Y and their induction by pro-inflammatory cytokines may favor the perpetuation of the inflammatory environment that disrupts the salivary glandular homeostasis in SS patients.Fondecyt-Chile 1120062 1130250 CONICYT-FONDAP 15130011 CONICYT/Programa de Investigacion Asociativa (ACT) 1111 Conicyt-Chil

Development of a small panel of SNPs to infer ancestry in chileans that distinguishes Aymara and Mapuche components

Background Current South American populations trace their origins mainly to three continental ancestries, i.e. European, Amerindian and African. Individual variation in relative proportions of each of these ancestries may be confounded with socio-economic factors due to population stratification. Therefore, ancestry is a potential confounder variable that should be considered in epidemiologic studies and in public health plans. However, there are few studies that have assessed the ancestry of the current admixed Chilean population. This is partly due to the high cost of genome-scale technologies commonly used to estimate ancestry. In this study we have designed a small panel of SNPs to accurately assess ancestry in the largest sampling to date of the Chilean mestizo population (n = 3349) from eight cities. Our panel is also able to distinguish between the two main Amerindian components of Chileans: Aymara from the north and Mapuche from the south. Results A panel of 150 ancestry-informative markers (AIMs) of SNP type was selected to maximize ancestry informativeness and genome coverage. Of these, 147 were successfully genotyped by KASPar assays in 2843 samples, with an average missing rate of 0.012, and a 0.95 concordance with microarray data. The ancestries estimated with the panel of AIMs had relative high correlations (0.88 for European, 0.91 for Amerindian, 0.70 for Aymara, and 0.68 for Mapuche components) with those obtained with AXIOM LAT1 array. The country's average ancestry was 0.53 +/- 0.14 European, 0.04 +/- 0.04 African, and 0.42 +/- 0.14 Amerindian, disaggregated into 0.18 +/- 0.15 Aymara and 0.25 +/- 0.13 Mapuche. However, Mapuche ancestry was highest in the south (40.03%) and Aymara in the north (35.61%) as expected from the historical location of these ethnic groups. We make our results available through an online app and demonstrate how it can be used to adjust for ancestry when testing association between incidence of a disease and nongenetic risk factors. Conclusions We have conducted the most extensive sampling, across many different cities, of current Chilean population. Ancestry varied significantly by latitude and human development. The panel of AIMs is available to the community for estimating ancestry at low cost in Chileans and other populations with similar ancestry.FONDEF D10I1007 D10E100