59 research outputs found
Phenylketonuria in Portugal: Genotype-Phenotype Correlations Using Molecular, Biochemical, and Haplotypic Analyses
The impairment of the hepatic enzyme phenylalanine hydroxylase (PAH) causes elevation of phenylalanine levels in blood and other body fluids resulting in the most common inborn error of amino acid metabolism (phenylketonuria). Persistently high levels of phenylalanine lead to irreversible damage to the nervous system. Therefore, early diagnosis of the affected individuals is important, as it can prevent clinical manifestations of the disease.info:eu-repo/semantics/publishedVersio
α-thalassaemia
Alpha-thalassaemia is inherited as an autosomal recessive disorder characterised by a microcytic hypochromic anaemia, and a clinical phenotype varying from almost asymptomatic to a lethal haemolytic anaemia
Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach
We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases
Recent developments in genetics and medically assisted reproduction : from research to clinical applications
Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.Peer reviewe
Contemporary management of TMJ involvement in JIA patients and its orofacial consequences
Exploring Factors Effecting the Continuance of Purchasing Behavior in Internet Shopping: Extrinsic Benefits and Intrinsic Benefits
A high incidence of mutations in exon 6 of the low-density lipoprotein receptor gene in Greek familial hypercholesterolemia patients, including a novel mutation
Analysis of low density lipoprotein receptor gene mutations and microsatellite haplotypes in Greek FH heterozygous children: six independent ancestors account for 60% of probands
This study reports the characterization of 60% of low density
lipoprotein receptor (LDLR) gene mutations in 150 unrelated Greek
familial hypercholesterolaemia (FH) heterozygous children by the
analysis of six LDLR gene mutations. The linkage disequilibrium of two
polymorphic microsatellites (D19S394 and D19S221) flanking the LDLR gene
on chromosome 19 to the four most common mutations strongly suggests
that each mutation is identical-by-descent in the probands included in
this study (this is also supported by the geographical distribution of
FH families with these mutations throughout Greece) and permits an
estimation of the number of generations from a common ancestor for each
mutation. The characterization of 60% of LDLR mutations in a
representative sample of Greek FH heterozygotes provides a basis for the
diagnosis of FH through DNA analysis in Greece, by using single-strand
conformation polymorphism analysis followed by allele-specific
oligonucleotide hybridization (exon 6 mutations) or restriction
endonuclease analysis (C152R, V408M). A rapid diagnostic assay positive
for the mutation has been developed for the most common mutation, G528D.
The application of simple DNA diagnostic assays for LDLR mutation
analysis are appropriate for the early identification of FH
heterozygotes in Greece and are useful for the primary prevention of
coronary artery disease
Noninvasive prenatal diagnosis of β-thalassaemia using individual fetal erythroblasts isolated from maternal blood after enrichment
Single nucleated red blood cells (NRBCs) isolated from maternal circulation were used for prenatal diagnosis of β-thalassaemia. The study included 22 pregnant women in the first trimester, 6 carriers at risk for β-thalassaemia and 16 noncarriers. Methodology involved enrichment of NRBCs by magnetic cell sorting (MACS) and microdissection of single NRBCs with a laser micromanipulation system. Single-cell genotyping based on nested real-time PCR for genotyping β-globin gene mutations was performed followed by a multiplexed minifingerprinting to confirm the origin of the isolated cells and possible contamination. Two polymorphic markers (D13S314 and GABRB3) facilitated the identification of fetal NRBCs through comparison of allele sizes found in the respective parents. In this study, 224 single NRBCs were detached and transferred into individual PCR tubes. Allele amplification in at least one microsatellite marker was achieved in 128/224 cells. Minifingerprinting analysis showed that 22 cells were fetal, 26 maternal and 80 were noninformative due to ADO or homozygosity. In 6 NRBCs the β-globin gene was amplified and in 2, coming from the same pregnancy, only the paternal mutation was detected. The low PCR success when genotyping isolated NRBCs was possibly due to the poor quality of fetal NRBCs and the relatively large size of the β-globin gene product. Copyright © 2007 John Wiley & Sons, Ltd
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