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Objective: We investigated the presence of cognitive biases in people with a recent-onset psychosis (ROP), schizophrenia and healthy adolescents and explored potential associations between these biases and psychopathology., Methods: Three groups were studied: schizophrenia (N=63), ROP (N=43) and healthy adolescents (N=45). Cognitive biases were assessed with the Cognitive Biases Questionnaire for Psychosis (CBQ). Positive, negative and depressive symptoms were assessed with the PANSS and Calgary Depression Scale (ROP; schizophrenia) and with the CAPE-42 (healthy adolescents). Cannabis use was registered. The association between CBQ and psychopathology scales was tested with multiple linear regression analyses., Results: People with schizophrenia reported more cognitive biases (46.1±9.0) than ROP (40±5.9), without statistically significant differences when compared to healthy adolescents (43.7±7.3). Cognitive biases were significantly associated with positive symptoms in both healthy adolescents (Standardized β=0.365, p=0.018) and people with psychotic disorders (β=0.258, p=0.011). Cognitive biases were significantly associated with depressive symptoms in healthy adolescents (β=0.359, p=0.019) but in patients with psychotic disorders a significant interaction between schizophrenia diagnosis and CBQ was found (β=1.804, p=0.011), which suggests that the pattern differs between ROP and schizophrenia groups (positive association only found in the schizophrenia group). Concerning CBQ domains, jumping to conclusions was associated with positive and depressive symptoms in people with schizophrenia and with cannabis use in ROP individuals. Dichotomous thinking was associated with positive and depressive symptoms in all groups., Conclusions: Cognitive biases contribute to the expression of positive and depressive symptoms in both people with psychotic disorders and healthy individuals., (Copyright © 2020. Publicado por Elsevier España, S.L.U.)

Introduction: Cognitive deficits are a cause of functional disability in psychotic disorders. Cognitive remediation therapy (CRT) might be applied to improve these deficits. We conducted a pilot study to explore whether thyroid hormones might predict the response to CRT in patients with recent-onset psychosis (ROP)., Methods: Twenty-eight stable ROP outpatients (9 women) were randomized to receive computerized CRT (N=14) or treatment as usual (TAU) (N=14), over three months. Both cognitive and thyroid functions were assessed at the baseline and after those three months to all patients. A full cognitive battery (CANTAB) was administered before and after the treatment. Serum levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were measured. FT4 concentrations were recoded into a dichotomic variable (FT4 group) based on the median of the sample (1.2 ng/dL). Data were analyzed on an intention-to-treat basis with linear mixed models. Afterwards, we offered CRT to all participants from the TAU group and seven enrolled CRT, reassessing them when finished. Secondary analyses were repeated in a sample of 14 participants who completed the CRT (either from the beginning or after the TAU period) and attended at least one third of the sessions., Results: The linear mixed models showed a significant time x CRT x FT4 group effect in two cognitive tasks dealing with executive functions and sustained attention (participants with higher FT4 concentrations worsened executive functions but improved sustained attention after CRT). In the secondary analysis including all patients assigned to CRT, higher FT4 concentrations were associated with a poorer response in verbal memory but a better response in spatial working memory., Conclusions: Free thyroxine concentrations moderate the response to a CRT in patients with early psychosis., (Copyright © 2020 Estrada, Crosas, Ahuir, Pérez-Muñoz, Zabala, Aguayo, Barbero, Montalvo, Tost, Llauradó, Guardia, Palao, Monreal and Labad.)

Background: It is possible that genes on the X chromosome are expressed differently depending of its parental origin. The objective of this study was to determine the influence of the parental origin of the X-chromosome on phenotypic variability, response to rhGH and on the biochemical profile of TS patients., Methods: This was a cross-sectional multicenter correlational study carried out over three years in six Latin-American university hospitals. Unrelated 45,X TS patients (n =  93; 18.3 ± 8.5 years )) were evaluated. A subgroup (n =  34) of the patients were prospectively treated with rhGH over two years. DNA profiles of patients and their mothers were compared to determine the parental origin of the retained X-chromosome through 10 polymorphic X-chromosome-STRs. The association with clinical features, biochemical profiles and anthropometric data at the beginning and after two years of rhGH treatment was determined., Results: Seventy two percent of patients retained the maternal X chromosome (Xm). A trend towards significance between maternal height and patients final height (p ≤ 0.07) in 45,Xm subjects was observed. There was no correlation between paternal height and patient height. No differences were detected between both groups in regard to dysmorphic features, classical malformations or increase in the height-SDS after rhGH. There were higher levels of triglycerides, total and LDL cholesterol in patients >20 years who retained the Xm., Conclusions: The parental origin of the retained X chromosome may influence lipid metabolism in TS patients, but its effect on growth seems to be minimal. No parental-origin-effect on the phenotypic features, associated anomalies and on the growth response to rhGH was found in 45,X TS individuals.

Background: The toxicity related to thiopurine drug therapy for inflammatory bowel disease (IBD) varies widely among patients. Almost 15-30% of patients with IBD develop side effects during treatment, often bone marrow suppression. Several factors have been implicated in determining this toxicity, mainly individual genetic variation related to formation of active thiopurine metabolites. The aim was to identify genes involved in thiopurine-related myelosuppression., Materials & Methods: A two-stage investigation of 19,217 coding SNPs (cSNPs) was performed in a Spanish (Inflammatory Bowel Disease Group of Galicia [EIGA]) cohort of 173 IBD patients, 15 with bone marrow suppression. The top 20 cSNPs identified in the first stage with p < 10(-3) for allelic test association and SNPs that define the common TPMT alleles were replicated in a different Spanish (ENEIDA) cohort (87 patients, 29 with bone marrow suppression)., Results: Several cSNPs showed a significant p-value in the allelic joint analysis (p-Cochran-Mantel-Haenszel test ≤2.55 × 10(-3)) despite no cSNP passing correction for multiple testing in the first cohort. Of note is rs3729961 in the gene IL6ST, a transducer signal chain shared by many cytokines including IL6 (p-value combined = 2.36 × 10(-4), odds ratio [95% CI]: 3.41 [1.71-6.78]). In addition, we detected association with rs3749598 in the FSTL5 gene that appears to interact with metalloproteases at the extracellular matrix level (p-value combined = 4.89 × 10(-4)), odds ratio (95% CI): 3.67 (1.68-8.01)., Conclusion: We have identified IL6ST and FSLT5 as new bone marrow suppression susceptibility candidate genes after thiopurine treatment in IBD patients. This is the first report of variants associated with thiopurine-related myelosuppression that was identified by a genome-wide association study. Its validation awaits functional analyses and replication in additional studies. Original submitted 14 September 2012; Revision submitted 13 February 2013.

Most individuals throughout the Americas are admixed descendants of Native American, European, and African ancestors. Complex historical factors have resulted in varying proportions of ancestral contributions between individuals within and among ethnic groups. We developed a panel of 446 ancestry informative markers (AIMs) optimized to estimate ancestral proportions in individuals and populations throughout Latin America. We used genome-wide data from 953 individuals from diverse African, European, and Native American populations to select AIMs optimized for each of the three main continental populations that form the basis of modern Latin American populations. We selected markers on the basis of locus-specific branch length to be informative, well distributed throughout the genome, capable of being genotyped on widely available commercial platforms, and applicable throughout the Americas by minimizing within-continent heterogeneity. We then validated the panel in samples from four admixed populations by comparing ancestry estimates based on the AIMs panel to estimates based on genome-wide association study (GWAS) data. The panel provided balanced discriminatory power among the three ancestral populations and accurate estimates of individual ancestry proportions (R² > 0.9 for ancestral components with significant between-subject variance). Finally, we genotyped samples from 18 populations from Latin America using the AIMs panel and estimated variability in ancestry within and between these populations. This panel and its reference genotype information will be useful resources to explore population history of admixture in Latin America and to correct for the potential effects of population stratification in admixed samples in the region., Competing Interests: CB and EGB are on the Scientific Advisory Board of 23andme's project "Roots into the Future." 23andme is a Mountain View, CA, company that provides direct-to-consumer genetic products. CB is also on the SAB of Ancestry.com, a company in Provo, UT, that provides direct-to-consumer genetic products. Neither company played a part in the research described here or has a financial stake in the results. The remaining authors have declared that no competing interests exist.

Haemophilia A and B are considered sex-linked inherited diseases caused by mutations in genes that encode factors VIII and IX, respectively. This results in the deficiency of these proteins plasma levels which are actively involved in the mechanism of blood coagulation. It has been reported that several mutations are responsible for the alteration of these genes, which is why the application of a molecular diagnostic method for the direct identification of female carriers is impractical. An appropriate diagnostic strategy is the indirect analysis of polymorphisms linked to the gene. The aim of this study was to identify female carriers in different families with history of HA and HB that live in Zulia State, Venezuela, characterizing intragenic gene polymorphisms of the clotting factors VIII and IX, which helped to identify and assign haplotypes, to diagnose or to exclude the carrying condition, to 95% of women who were needing the study for HA and to 100% for HB.

Prostate Cancer (CAP), is a complex disease with a multifactorial origin. It is characterized by heterogenous patterns of growth of neoplasic tissue, varying widely in its progression, age of beginning and therapy response. It is considered as the second most common cause of death by cancer in men and, it has been estimated, that one of five, suffers of CAP through the course of his life. The genetic etiology of neoplasic transformation of normal prostate cells is still not known; nevertheless, investigations in epidemiology have demonstrated a strong genetic component in its development, suggesting so much a pattern of mendelian inheritance as the presence of loci of susceptibility throughout the human genome. It has been described a cromosomic location related to the CAP in locus 1q24-25, denominated HPC1, where the gene RNASEL is located, and the seggregation of its alleles has been associated with the development of CAP in numerous familiar groups. The RNASEL gene codifies for a ribonuclease protein that degrades vi-ral and cellular ARN and takes part in the apoptosis. A decrease of the enzymatic activity up to three times in carriers of the G1385A polymorphism of this gene has been reported, and the same has been associated frequently with the development of CAP. Using a variant of the Polymerase Chain Reaction, Allele specific amplification, this investigation had as objective to determine the association between variant G1385A and CAP, in a sample of 103 masculine individuals with and without CAP, pertaining to the population of Maracaibo, Venezuela. An association between these variants and CAP could not be demonstrated.

The pathogenesis of recurrent spontaneous abortion is multifactorial, presumably involving the interaction of several genetic and environmental factors. The methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism has been implicated as risk factor for recurrent spontaneous abortion (RA). The main objective of this research was to investigate the association between the C677T polymorphism of the MTHFR gene as a genetic risk factor for idiopathic RA. Molecular analysis was performed in 80 DNA samples from 30 patients with RA and among 50 healthy control subjects. Using the Polymerase Chain Reaction (PCR), a 198 bp (bases pairs) fragment, was digested with the restriction enzyme Hinf1, which can recognize the C > T substitution responsible for the polymorphism. 677T MTHFR allele frequencies for group with RA and the control group were 35% and 33%, respectively and 677C MTHFR allele frequencies were 65% and 67%, respectively. There was no significant difference in allele frequency between these two groups. The data presented in this study fail to support the relationship between MTHFR C677T polymorphism and risk in women with RA.

Mutations in the K-ras oncogene are common in colo-rectal cancer, which affect the biological behaviour and may influence the susceptibility to therapy in these tumors. The objective of this work was to identify the types of K-ras mutations observed in referred patients with colo-rectal cancer and to relate them to their degree of histological differentiation and clinical stage. Histopathological and clinical data were obtained from medical records. DNA was obtained from both, fresh tissue and tumor tissue embedded in paraffin. The K-ras gene was amplified through the polymerase chain reaction (PCR) and the amplified fragments were digested with restriction enzymes. We found mutations in codons 12 and 13 of the K-ras oncogene in 23.33% of patients. Of these, 28.57% were located at codon 12, 57.14% were at codon 13 and 14.29% at both codons. They were more frequent in tumors located in the left hemicolon and, according to their histological type, were more frequent in well differentiated adenocarcinomas (58.70%) and in mucinous (28.57%). The identified mutations were more frequent in advanced stages (C2) of Dukes' classification. The molecular analysis of the K-ras oncogene made mutations evident, which could be useful in the diagnosis and prognosis of colorectal tumors. The frequency of mutations found in this work is similar to some of those reported worldwide; however, they differ in the more frequent type of mutation, which, in our study, was located at codon 13 in more than 50% of the cases.

Haemophilia A (HA) and B (HB) are the most common inherited bleeding diseases. HA and HB are X-linked recessive disorders caused by mutation in the factor VIII gene which maps to Xq28 and factor IX located at Xq27, respectively; resulting in absence or deficiency of these proteins. Several mutations have been reported as responsible for the disturbance of these genes; therefore, the use of direct molecular techniques to analyze the carrier status of women and their affected fetuses in not easy to perform. Thus, gene linked polymorphisms analysis is the most convenient molecular test since it is independent from the nature of the mutation, allowing the identification of the mutant X chromosome by following its segregation along the pedigree. The main objective of this research was to perform the molecular diagnosis of HA or HB carrier status in pregnant women and male fetuses affected or not, who were referred to the Medical Genetic Unit of the University of Zulia (UGM-LUZ), Maracaibo, Venezuela. Molecular analysis for HA and HB was performed in 32 DNA samples from 8 pregnant women, 8 fetuses, 8 affected and 8 healthy males. Using the Polymerase Chain Reaction (PCR), a 142 bp (bases pairs) fragment, which corresponds to intron 18 of the Factor VIII gene, was amplified. This fragment has a restriction polymorphism for the enzyme Bcl I. Additionally, a Duplex PCR was performed for the STRs (short tandem repeat) of introns 13 and 22 of the same gene. On the other hand, Hinf I, Xmn I y Taq I polymorphism in the factor IX gene were also amplified, so, we were able to build the haplotypes for each one of the key members in the families affected. The latter, allowed us to identify, in five of the eight cases, the mutant X chromosome responsible of HA and HB, thus, prenatal diagnosis was possible with the following results: three healthy males fetuses, two affected males fetuses with HA and three females fetuses.

The distribution of allele frequencies and haplotypes for 12 STRs loci, (DYS19, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DYS385a/b, DYS437, DYS438 and DYS439) on the Y-chromosome from two Venezuelan populations were determined in 173 DNA samples of unrelated males living in Caracas (62) and Maracaibo (111). Some parameters of forensic importance were calculated. AMOVA and genetic distances between these populations were estimated. The results confirmed Y-STR genotypes as useful markers for forensic genetics analysis.

Osteoporosis (OP) is an important public issue affecting more than 150 millions all over the world, mainly post-menopausic women. Epidemiological studies have shown that the genetic factors could be involved in 80-90% of the bone mineral density variabiblity and therefore, related to the risk of OP manifestations. The vitamin D receptor (VRD) gene has been extensively studied, but its relationship with OP has been controversial. The aim of this investigation was to study the association of Bsm I, Apa I and Taq I VDR gene polymorphism with OP in 147 post-menopausic women; 71 with OP and 76 without the disease (control). The molecular gene analysis was performed using the polymerase chain reaction (PCR). The genotypes BB, AA, and tt were found in 56.33, 50.70 and 25.35% and in 21.05, 28.95 and 10.53% of OP patients and controls respectively. The haplotype BBAAtt was observed in 23.94% of OP patients and 5.26% of the controls. This haplotype was a risk factor for OP, since a odds ratio (OR) of 5.66 was found, while, haplotype BbaaTT was a protection factor (OR: 0.10). These findings support the association of the vitamin D receptor gene BBAAtt haplotype with OP.

Autism is a complex neurodevelopmental disorder characterized by impairment of social interaction, language, communication, and stereotyped, repetitive behavior. Genetic predisposition to Autism has been demonstrated in families and twin studies. There is evidence (linkage and genetic association, biochemical, neuropathological, functional and cytogenetic) that the gamma-amino-butyric acid receptor beta 3 subunit gene (GABRB3) at 15q11-q13 is a susceptibility candidate gene for Autism. The aim of this exploratory study was to identify new variants of this gene. We performed the molecular analysis (SSCP/Sequencing) of 10 exons and its intronic flanking regions of GABRB3, using a candidate gene screening approach in 18 idiopathic autistic patients. We did not find non-synonymous mutations at the encoding regions, but we identified four SNP (Single Nucleotide Polymorphism). The first one, represented a silent mutation p.P25P in exon la and was found in 33.33% of the patients. The second one: IVS3 + 13C > T (5b far from the intron 5' consensus sequence), was found in 44.44% of the patients, while it was also identified in 16.67% of the controls. Simultaneously, 33.33% of the patients had both variants, and although, 16.67% of the controls also had the same combination of variants, 66.66% of the patients with those alleles had a familiar history of Autism. The third and fourth SNP: IVS5 + 40T > G and IVS-70A > G were identified in two different patients. None of the last three SNPs have been reported at the SNP database (dbSNP). The proximity of SNP: IVS3 + 13C > T with the consensus and interaction sequence with U1 nucleoriboprotein, could disturb the normal splicing of mRNA. This is in agreement with the evidence of lower levels of GABA-A receptors in autistic brains; so, it could be a common variant, that by itself could not cause a phenotypic effect, but joined to other variants with the same gene, in different related genes or with epigenetic changes, could explain the autistic phenotype and its heterogeneity.

Today infertility is a major health problem affecting about 10-20% of couples. A male factor is assumed to be responsible in about 50% of the infertile couples. The origin of reduced testicular sperm function is unknown in about 60-70% of cases. There are several causes of male infertility such as varicocele, spermatic duct obstruction, and endocrine disorders. Micro-deletions in the Yq are known to represent the pathogenic mechanisms for infertile males. Three different non-overlapping regions designated as AZFa, AZFb, and AZFc are located in interval 5-6 of Yq, and are associated with impaired spermatogenesis in humans. To determine the prevalence of Y chromosomal microdeletions in Venezuelan males with idiopathic infertility, chromosomal, seminal, histological and molecular analyses were carried out in 29 Venezuelan males with idiopathic azoospermia or oligoospermia. Y-microdeletions analyses were performed using a multiplex polymerase chain reaction (PCR)-based technique with 22 sequences-tagged-sites (STSs). One of 29 patients (3.4%) had Yq microdeletions on AZFc. The frequency of AZF microdeletions in Venezuelan patients was similar to other populations with different ethnical or geographical origin.

Allele frequencies for 15 short tandem repeats (STRs) autosomal loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA, included in the AmpFLSTR Identifiler, Applied Biosystems) were studied in the city of Maracaibo, Venezuela and were compared with other published Latin-American populations for the same loci. Population and forensic parameters were estimated.

Cystic Fibrosis (CF) is the most common and severe autosomal recessive disease in Caucasian populations, with an incidence of 1 in 2500 live births. It is characterized by a generalized disturbance in exocrine glands and it is caused by over one thousand mutations at the cystic fibrosis conductance regulator gene (CFTR) mapped at 7q31. AF508 is the most frequent mutation worldwide and it consists in a deletion of the codon that encodes fenilalanine at the 508 protein's position. The aim of this study was to determine the frequency of the delta F508 mutation in Venezuelan patients with CF using the Polymerase Chain Reaction (PCR). We studied thirty patients of twenty eight families who were diagnosed with CF based on their clinical features and sweat chloride level > 60 mEq/l in two determinations. Detection of the mutation was performed from the amplification of a 98 pair of bases (pb) CF gene segment which contains the codon that encodes fenilalanine in the 508 position by PCR. This PCR product is absent in those who have the mutation. The delta F508 allelic frequency was 26.79%, distributed in six homozygous and seven compound heterozygote delta F508/X. The reminder mutations (no delta F508) represent 73.21%. The delta F508 frequency in our sample is less than the reported in European countries. On the other hand, a delta F508 frequency highly heterogeneous has been observed in Latin-American countries. This variation results from mixed populations with a different genetic background influenced by external migration and CF molecular alterations, which exists in the analyzed populations. In this study, the delta F508 mutation comes mainly from grandparents (79.41%) who were born in Mediterranean countries and Colombia, while the no delta F508 mutations come from grandparents who were born in Venezuela (79.27%) and Colombia (17.07%).

Among genes implied on the osteoporosis genetics, the most studied gene worldwide is the receptor gene of D vitamin (VDR), through the characterization of Bsm I polymorphism. The main objective of this research was to analyze the Bsm I polymorphism of the VDR gene in a sample of 133 postmenopausal women distributed in three groups: 54 with osteoporosis, 24 with osteopenia and 55 normal controls for the disease. 28 of the women with osteoporosis presented the BB genotype, which is related in other countries to bone mineral density decrease, 20 had the Bb genotype, and 6 the bb genotype. Of the control group only 11 women presented the BB genotype, 36 showed the heterozygote genotype and 8 the bb genotype. The frequencies of the B and b alleles in the analyzed population were 0.6 and 0.4 respectively. The BB genotype was found in 52% of the group with osteoporosis, and in 20% of the control group, these findings are statistically significant, which suggest an association between the BB genotype and osteoporosis.