PubMed | University of Calgary, Reykjavik University, McMaster University, Fetal Medicine Unit and 10 more.
Type: Journal Article | Journal: European journal of human genetics : EJHG | Year: 2016
Non-invasive prenatal testing is increasingly available worldwide and stakeholder viewpoints are essential to guide implementation. Here we compare the preferences of women and health professionals from nine different countries towards attributes of non-invasive and invasive prenatal tests for Down syndrome. A discrete choice experiment was used to obtain participants stated preference for prenatal tests that varied according to four attributes: accuracy, time of test, risk of miscarriage, and type of information. Pregnant women and health professionals were recruited from Canada, Denmark, Iceland, Israel, Italy, the Netherlands, Portugal, Singapore, and the United Kingdom. A total of 2666 womens and 1245 health professionals questionnaires were included in the analysis. Differences in preferences were seen between women and health professionals within and between countries. Overall, women placed greater emphasis on test safety and comprehensive information than health professionals, who emphasised accuracy and early testing. Differences between womens and health professionals preferences are marked between countries. Varied approaches to implementation and service delivery are therefore needed and individual countries should develop guidelines appropriate for their own social and screening contexts.
PubMed | Registro Nacional de ADN, Laboratorio Of Genetica Forense, University Miguel Hernández, Forensic Science Unit and 37 more.
Type: | Journal: Forensic science international. Genetics | Year: 2016
Since 1992, the Spanish and Portuguese-Speaking Working Group of the ISFG (GHEP-ISFG) has been organizing annual Intercomparison Exercises (IEs) coordinated by the Quality Service at the National Institute of Toxicology and Forensic Sciences (INTCF) from Madrid, aiming to provide proficiency tests for forensic DNA laboratories. Each annual exercise comprises a Basic (recently accredited under ISO/IEC 17043: 2010) and an Advanced Level, both including a kinship and a forensic module. Here, we show the results for both autosomal and sex-chromosomal STRs, and for mitochondrial DNA (mtDNA) in two samples included in the forensic modules, namely a mixture 2:1 (v/v) saliva/blood (M4) and a mixture 4:1 (v/v) saliva/semen (M8) out of the five items provided in the 2014 GHEP-ISFG IE. Discrepancies, other than typos or nomenclature errors (over the total allele calls), represented 6.5% (M4) and 4.7% (M8) for autosomal STRs, 15.4% (M4) and 7.8% (M8) for X-STRs, and 1.2% (M4) and 0.0% (M8) for Y-STRs. Drop-out and drop-in alleles were the main cause of errors, with laboratories using different criteria regarding inclusion of minor peaks and stutter bands. Commonly used commercial kits yielded different results for a micro-variant detected at locus D12S391. In addition, the analysis of electropherograms revealed that the proportions of the contributors detected in the mixtures varied among the participants. In regards to mtDNA analysis, besides important discrepancies in reporting heteroplasmies, there was no agreement for the results of sample M4. Thus, while some laboratories documented a single control region haplotype, a few reported unexpected profiles (suggesting contamination problems). For M8, most laboratories detected only the haplotype corresponding to the saliva. Although the GHEP-ISFG has already a large experience in IEs, the present multi-centric study revealed challenges that still exist related to DNA mixtures interpretation. Overall, the results emphasize the need for further research and training actions in order to improve the analysis of mixtures among the forensic practitioners.
Torres F.,CGC Genetics |
Torres F.,Abel Salazar Biomedical Sciences Institute |
Barbosa M.,Mount Sinai School of Medicine |
Barbosa M.,Instituto Gulbenkian Of Ciencia |
And 2 more authors.
Journal of Medical Genetics | Year: 2016
Neurodevelopmental disorders (NDs) encompass a spectrum of neuropsychiatric manifestations. Chromosomal regions 1q21.1, 3q29, 15q11.2, 15q13.3, 16p11.2, 16p13.1 and 22q11 harbour rare but recurrent CNVs that have been uncovered as being important risk factors for several of these disorders. These rearrangements may underlie a broad phenotypical spectrum, ranging from normal development, to learning problems, intellectual disability (ID), epilepsy and psychiatric diseases, such as autism spectrum disorders (ASDs) and schizophrenia (SZ). The highly increased risk of developing neurodevelopmental phenotypes associated with some of these CNVs makes them an unavoidable element in the clinical context in paediatrics, neurology and psychiatry. However, and although finding these risk loci has been the goal of neuropsychiatric genetics for many years, the translation of this recent knowledge into clinical practice has not been trivial. In this article, we will: (1) review the state of the art on recurrent CNVs associated with NDs, namely ASD, ID, epilepsy and SZ; (2) discuss the models used to dissect the underlying neurobiology of disease, (3) discuss how this knowledge can be used in clinical practice.
Tavares P.,CGC Genetics |
Tavares P.,Rua Sa da Bandeira no. 706 1 |
Dias L.,CGC Genetics |
Dias L.,Rua Sa da Bandeira no. 706 1 |
And 5 more authors.
Personalized Medicine | Year: 2011
We advocate a new paradigm for genetic diagnosis based on using customized array panels, each of which groups multiple genes and mutations associated with clinical profiles that are common to particular syndromic diseases. This parallel approach, based on a single-test multigene multiplexing strategy, compared with traditional sequential testing by gene-by-gene genetic analysis, drastically reduces the time and cost of diagnosis while maintaining accuracy and reliability. Faster diagnosis enables early decision-making to facilitate better patient management and outcomes at reduced costs to the healthcare system. © 2011 Future Medicine Ltd.
Melo C.,Centro Hospitalar do Medio Ave |
Gama-de-Sousa S.,Centro Hospitalar do Medio Ave |
Almeida F.,Centro Hospitalar do Medio Ave |
Rendeiro P.,CGC Genetics |
And 3 more authors.
Gene | Year: 2013
Cat eye syndrome is a rare congenital disease characterized by the existence of a supernumerary chromosome derived from chromosome 22, with a variable phenotype comprising anal atresia, coloboma of the iris and preauricular tags or pits. We report a girl with cat eye syndrome, presenting short stature, with growth hormone deficiency due to posterior pituitary ectopia. Short stature is a common feature of this syndrome, and the association with a structural pituitary anomaly has been described, however growth hormone deficiency and the underlying mechanisms are rarely reported. A review on short stature and growth hormone deficiency in cat eye syndrome is conducted. © 2013 Elsevier B.V.
Pereira I.,University of Porto |
Vaz P.,University of Porto |
Almeida R.F.,University of Porto |
Tavares P.,CGC Genetics |
And 2 more authors.
Revista Portuguesa de Estomatologia, Medicina Dentaria e Cirurgia Maxilofacial | Year: 2014
Clinically it appears that some patients with etiological factors (dental pathology in the maxillary sinus) exhibit sinus disease and others do not. The aim of this paper is to present the case of a female patient, with a periapical lesion, with symptoms of sinus pathology and the possibility of genetic influence on exacerbated response in the presence of the maxillary sinus pathology of dental origin, through genetic sequencing of IRAK4 gene.The surgical procedure was performed under general anaesthesia. The cyst was enucleated, the dental roots were extracted, a curettage and an irrigation with physiologic saline 0.9% were performed.This work opens new perspectives for research on the role of a specific polymorphism in the IRAK4 gene in the host response. Thus, it may provide valuable data for understanding the phenomena that underlie the recurrence of maxillary sinus pathology and also advance knowledge to improve therapeutic decisions. © 2014 Sociedade Portuguesa de Estomatologia e Medicina Dentária.
Braga A.C.,University of Minho |
Vaz P.,University of Porto |
Sampaio-Fernandes J.C.,University of Porto |
Felino A.,University of Porto |
Tavares M.P.,CGC Genetics
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2012
In this work we propose to build a set of binary logistic models that could assess the probability of success or no success in oral rehabilitation process taking into account some genetic factors, individual habits clinical and non-clinical factors. The study was conducted in a retrospective evaluation and consisted of 155 subjects undergoing oral rehabilitation in the Northern region of Portugal. We evaluated multiple factors in the construction of binary logistic regression models. We have chosen the model that gave statistically better discriminating power between success and failure, through the value of area under the ROC curve. The model that reveals better performance was Model 4, with AUC = 0.789 and a 95% confidence interval [0.715;0.863]. © 2012 Springer-Verlag.
Morais P.,Hospital S Joao |
Morais P.,University of Porto |
Mota A.,Hospital S Joao |
Mota A.,University of Porto |
And 7 more authors.
Dermatology Online Journal | Year: 2011
A 13-year-old boy, born prematurely and hypotonic, from non-consanguineous healthy parents, was referred to our department because of easy bruising. A slightly extensible, thin and translucent skin, associated with dysmorphic facies, acrogeria, multiple ecchymoses, hypermobility of the small joints, dorsal kyphosis, genu valgum, flat feet, elongated upper limbs, and low muscle tone were all evident. A history of learning disability and bilateral inguinal hernia was present. Blood and imaging studies were unremarkable. A skin biopsy disclosed an unremarkable dermis; electron microscopy showed abnormalities in the diameter, contour, and shape of collagen fibrils/fibers. Genetic analysis revealed heterozygosity for a novel mutation in COL3A1 gene (c.3527G>A), confirming the diagnosis of vascular Ehlers-Danlos syndrome (VEDS). The patient died at 15 years of age because of aortic dissection. Vascular Ehlers-Danlos syndrome is a rare, life-threatening, autosomal dominant variant of EDS, resulting from mutations in COL3A1 gene. Affected individuals are prone to serious and potentially fatal complications, especially vascular, intestinal, and uterine ruptures. Delay in diagnosis is common, even when the clinical presentation is typical. Therefore, dermatologists should be familiar with VEDS features because the skin findings may be the first signs. Early diagnosis will improve management of visceral complications and allow early genetic counseling. © 2011 Dermatology Online Journal.
PubMed | Scripps Research Institute, Hospital Pedro Hispano and CGC Genetics
Type: Journal Article | Journal: Journal of diabetes & metabolism | Year: 2016
Wolfram syndrome type 1 is a rare, autosomal recessive, neurodegenerative disorder that is diagnosed when insulin-dependent diabetes of non-auto-immune origin and optic atrophy are concomitantly present. Wolfram syndrome is also designated by DIDMOAD that stands for its most frequent manifestations: diabetes insipidus, diabetes mellitus, optic atrophy and deafness. With disease progression, patients also commonly develop severe neurological and genito-urinary tract abnormalities. When compared to the general type 1 diabetic population, patients with Wolfram Syndrome have been reported to have a form of diabetes that is more easily controlled and with less microvascular complications, such as diabetic retinopathy. We report a case of Wolfram syndrome in a 16-year-old male patient who presented with progressive optic atrophy and severe diabetes with very challenging glycemic control despite intensive therapy since diagnosis at the age of 6. Despite inadequate metabolic control he did not develop any diabetic microvascular complications during the 10-year follow-up period. To further investigate potential causes for this metabolic idiosyncrasy, we performed genetic analyses that revealed a novel combination of homozygous sequence variants that are likely the cause of the syndrome in this family. The identified genotype included a novel sequence variant in the Wolfram syndrome type 1 gene along with a previously described one, which had initially been associated with isolated low frequency sensorineural hearing loss (LFSNHL). Interestingly, our patient did not show any abnormal findings with audiometry testing.
PubMed | Cedars Sinai Medical Center, Hospital Universitario La Paz, Wake forest University, Pontifical Catholic University of Parana and 15 more.
Type: Journal Article | Journal: European journal of human genetics : EJHG | Year: 2015
Array comparative genomic hybridization (aCGH) is a powerful genetic tool that has enabled the identification of novel imbalances in individuals with intellectual disability (ID), autistic disorders and congenital malformations. Here we report a genotype first approach using aCGH on 13 unrelated patients with 19p13.3 submicroscopic rearrangement (11 deletions and 2 duplications) and review cases in the literature and in public databases. Shared phenotypic features suggest that these patients represent an interstitial microdeletion/microduplication syndrome at 19p13.3. Common features consist of abnormal head circumference in most patients (macrocephaly with the deletions and microcephaly with the duplications), ID with developmental delay (DD), hypotonia, speech delay and common dysmorphic features. The phenotype is associated with at least a ~0.113Mb critical region harboring three strong candidate genes probably associated with DD, ID, speech delay and other dysmorphic features: MAP2K2, ZBTB7A and PIAS4, an E3 ubiquitin ligase involved in the ubiquitin signaling pathways, which we hypothesize for the first time to be associated with head size in humans.