Institute Investigacion Sanitaria Of Santiago

Santiago de Compostela, Spain

Institute Investigacion Sanitaria Of Santiago

Santiago de Compostela, Spain
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Quintela I.,University of Santiago de Compostela | Barros F.,Grupo de Medicina Xenomica USC | Fernandez-Prieto M.,Institute Investigacion Sanitaria Of Santiago | Martinez-Regueiro R.,University of Santiago de Compostela | And 2 more authors.
American Journal of Medical Genetics, Part A | Year: 2015

The few proximal 4q chromosomal aberrations identified in patients with neurodevelopmental phenotypes that have been published to date are variable in type, size and breakpoints and, therefore, encompass different chromosome bands and genes, making the establishment of genotype-phenotype correlations a challenging task. Here, microarray-based copy number analysis allowed us the detection of two novel and partially overlapping deletions in two unrelated families. In Family 1, a 4q13.1-q13.2 deletion of 3.84Mb was identified in a mother with mild intellectual disability and in her two children, both with mild intellectual disability and attention deficit hyperactivity disorder. In Family 2, a de novo 4q13.2-q13.3 deletion of 6.81Mb was detected in a female patient, born to unaffected parents, with a diagnosis of mild intellectual disability, behavioral disorder and facial dysmorphism. The shortest region of overlap between these two aberrations is located at chromosome 4q13.2 and includes 17 genes amongst of which we suggest UBA6 (ubiquitin-like modifier-activating enzyme 6) as a strong candidate gene for these phenotypes. © 2015 Wiley Periodicals, Inc.


PubMed | University of Santiago de Compostela, Institute Investigacion Sanitaria Of Santiago and Grupo de Medicina Xenomica USC
Type: Case Reports | Journal: American journal of medical genetics. Part A | Year: 2016

The few proximal 4q chromosomal aberrations identified in patients with neurodevelopmental phenotypes that have been published to date are variable in type, size and breakpoints and, therefore, encompass different chromosome bands and genes, making the establishment of genotype-phenotype correlations a challenging task. Here, microarray-based copy number analysis allowed us the detection of two novel and partially overlapping deletions in two unrelated families. In Family 1, a 4q13.1-q13.2 deletion of 3.84Mb was identified in a mother with mild intellectual disability and in her two children, both with mild intellectual disability and attention deficit hyperactivity disorder. In Family 2, a de novo 4q13.2-q13.3 deletion of 6.81Mb was detected in a female patient, born to unaffected parents, with a diagnosis of mild intellectual disability, behavioral disorder and facial dysmorphism. The shortest region of overlap between these two aberrations is located at chromosome 4q13.2 and includes 17 genes amongst of which we suggest UBA6 (ubiquitin-like modifier-activating enzyme 6) as a strong candidate gene for these phenotypes.


PubMed | Hospital Clinico Universitario Of Santiago Of Compostela, Institute Investigacion Sanitaria Of Santiago and Neonatal Unit
Type: Journal Article | Journal: American journal of clinical pathology | Year: 2016

To establish a genetic and clinical diagnosis in a newborn with fetal-onset dilated cardiomyopathy using next-generation sequencing technologies.We have conducted the clinical evaluation of the proband and the molecular characterization of his disease by means of whole-exome sequencing. In addition, the clinical evaluation and subsequent genetic screening of five relatives has been performed. This comprises two males with features of left ventricular noncompaction cardiomyopathy, two females suspected of being carriers, and one pregnant female at risk of being a carrier and thereby transmitting the disease to her child.We have discovered a novel variant in the TAZ gene by means of whole-exome sequencing. This, together with the performance of further clinical analyses, led to an early diagnosis of Barth syndrome in the proband. The genetic screening of the subjects familial group revealed full cosegregation of the variant with another two affected males and identified several female carriers.The investigation for Barth syndrome must be considered in male babies and young boys with dilated cardiomyopathy and left ventricular noncompaction. Next-generation sequencing technologies provide an accurate and rapid diagnostic tool in prospectively and retrospectively identifying individuals with this Mendelian syndrome.


Gimenez-Sanchez F.,Hospital Torrecardenas | Kieninger D.M.,Johannes Gutenberg University Mainz | Kueper K.,Johannes Gutenberg University Mainz | Martinon-Torres F.,University of Santiago de Compostela | And 11 more authors.
Vaccine | Year: 2011

Two randomized trials of 13-valent pneumococcal conjugate vaccine (PCV13) relative to PCV7 evaluated the immune responses of coadministered antigens comprising Infanrix ® hexa/Infanrix ®-IPV+Hib (diphtheria, tetanus, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b). After the 3-dose infant series, immunogenic noninferiority was demonstrated for all concomitantly administered antigens between the PCV13 and PCV7 groups. All antigens elicited good booster responses after the toddler dose except pertussis toxoid; however, 99.6% subjects achieved pertussis toxoid protective antibody level ≥5EU/mL in both groups. These results support the concomitant administration of PCV13 and Infanrix hexa/Infanrix-IPV+Hib as part of routine immunization schedules. © 2011 Elsevier Ltd.


Diez-Domingo J.,Centro Superior Of Investigacion En Salud Publica Csisp | Gurtman A.,Pfizer | Bernaola E.,Hospital Virgen Del Camino Of Pamplona | Gimenez-Sanchez F.,Hospital Torrecardenas | And 10 more authors.
Vaccine | Year: 2013

Background: Given the concurrent administration of multiple vaccines during routine pediatric immunizations, efforts to elucidate the potential interference of any vaccine on the immune response to the concomitantly administered antigens are fundamental to prelicensure clinical research. Methods: This phase 3 randomized controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) versus 7-valent PCV (PCV7) assessed immune responses of concomitantly administered meningococcal group C conjugated to diphtheria toxin cross-reactive material 197 (MnCCV-CRM197) in a 2-dose infant series and 15-month toddler dose. Results: 619 subjects were randomized, 315 to PCV13 and 304 to PCV7. MnCCV-CRM197-induced immune responses were similar between the PCV13 and PCV7 groups, with >97% of the subjects achieving a ≥1:8 meningococcal serum bactericidal assay (SBA) titer after both dose 2 and the toddler dose. Geometric mean titers were lower in the PCV13 group 191.22 (167.72, 218.02) versus 266.19 (234.86, 301.71) following dose 2 and 432.28 (361.22, 517.31) versus 730.84 (642.05, 831.91) following the toddler dose. The geometric mean (GM) meningococcal SBA titer ratios (PCV13/PCV7) were 0.72 after dose 2 and 0.59 after the toddler dose. The criteria for MnCCV-CRM197 non-inferiority for GM titers were satisfied after dose 2. Percent responders was similar up to titers of 1:128. PCV13 elicited substantial antipneumococcal responses against all 13 serotypes, with ≥90% of the subjects achieving an antibody concentration ≥0.35μg/mL after dose 3 in the infant series. Safety and tolerability were similar between the vaccine groups. Conclusions: Immunogenicity results of MnCCV-CRM197 for PCV13 compared with PCV7 included lower GMTs, but the clinical significance of this is unknown as the proportion of infants achieving protective MenC antibody titers was comparable in the two groups. Percent responders were similar up to titers of 1:128. PCV13 has an acceptable safety profile in infants and toddlers, while providing expanded coverage against pneumococcal disease. © 2013 Elsevier Ltd.


Gervaix A.,University of Geneva | Ansaldi F.,University of Genoa | Brito-Avo A.,Clinica Pediatrica | Azzari C.,University of Florence | And 7 more authors.
Clinical Therapeutics | Year: 2014

Nonadherence to recommended pneumococcal conjugate vaccine (PCV) schedules may have implications for protection against pneumococcal disease. In this commentary, we have assessed adherence to the recommended dosing schedules (the completion of the primary PCV and booster series) in different European countries. We found that adherence with the PCV schedule was lower than that for diphtheria-tetanus-acellular pertussis (DTaP) and that higher adherence was observed in countries where PCV vaccination is recommended and funded. Adherence with the booster dose is often lower than that with the primary series completion, and it is often given after the recommended age. These data highlight the need to encourage timely vaccination of children with PCV, in line with local immunization schedules. There is no single solution to improve adherence; actions need to be tailored to the context of individual countries through initiatives at the national, regional, and local levels and should target different stakeholders. © 2014 Elsevier HS Journals, Inc.


PubMed | University of Santiago de Compostela, Sanguine and Institute Investigacion Sanitaria Of Santiago
Type: | Journal: Forensic science international. Genetics | Year: 2014

French population, despite of its crucial geographic location for repopulation movements of Europe across time, it has been insufficiently characterized at the genetic level, especially for Y-chromosomal DNA variation. In order to make a genetic structure characterization, we have analyzed the Y-chromosome diversity of 558 male individuals, scattered along 7 different French regions: Alsace (Strasbourg), Auvergne (Clermont-Ferrand), Bretagne (Rennes), le-de-France (Paris), Midi-Pyrnes (Toulouse), Nord-Pas-de-Calais (Lille) and Provence-Alpes-Cte dAzur (Marseille). A total of 17 Y-chromosome STRs and 27 Y-chromosome SNPs were genotyped for each individual. Even though we find that most of the individual populations in France were not differentiated from each other, Bretagne population shows population substructure, an important fact to be considered when establishing general population databases.


PubMed | King Abdulaziz University, University of Valladolid, Hospital Clinico San Carlos, Institute Investigacion Sanitaria Of Santiago and 2 more.
Type: Journal Article | Journal: Ophthalmology | Year: 2015

To determine whether single nucleotide polymorphisms (SNPs) of genes coding for matrix metalloproteinases (MMPs) and the prostaglandin F2 receptor gene (PTGFR) are related to a response to latanoprost in a white Spanish population of glaucomatous patients.Case-control study.One hundred twenty-four patients with open-angle glaucoma.Genotyping was performed in 117 patients with primary open-angle glaucoma with a minimum treatment duration of 4 weeks. Candidate genes and individual polymorphisms were selected according to the effect on the mechanism of action of latanoprost. Multi-SNP haplotype analyses for associations also were tested.Diurnal intraocular pressure reduction and genotyping of the SNPs in the MMPs and PTGFR.The PTGFR SNPs were associated with positive (rs6686438, rs10786455) and negative (rs3753380, rs6672484, rs11578155) responses to latanoprost. Multiple testing found 2 genes, PTGFR and MMP-1, were related to refractoriness to latanoprost.The SNPs of the PTGFR and MMP-1 genes may determine the latanoprost response in a white European Spanish population. This study identified 5 SNPs related to the latanoprost response; 1 SNP, rs3753380, already has been associated with a poor response to latanoprost in a healthy Japanese population. Latanoprost is a commonly used antiglaucomatous drug, and increased knowledge of its mechanism of action will lead to advances in pharmacogenetics.


Rivero Calle I.,Institute Investigacion Sanitaria Of Santiago | Rodriguez-Tenreiro Sanchez C.,Institute Investigacion Sanitaria Of Santiago | Martinon-Torres F.,Institute Investigacion Sanitaria Of Santiago
Enfermedades Infecciosas y Microbiologia Clinica | Year: 2015

N. meningitidis is a major cause of meningitis and septicemia and a major public health problem in many countries. The disease, that can be fulminant, has a high mortality and may cause serious sequelae, even in cases of apparently optimal medical treatment. Chemoprophylaxis may prevent secondary cases among those in close contact with the ill, but, since secondary cases represent only 1%-2% of all meningococcal disease, chemoprophylaxis has a small impact when fighting most of endemic and epidemic forms. Given that al least 5% -15% of children and young adults are carriers, the fight against meningococcal disease based on chemotherapeutic elimination of nasopharyngeal colonization is virtually impossible. Therefore, immunization is the only rational way to combat this disease. © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica.


PubMed | Institute Investigacion Sanitaria Of Santiago
Type: Journal Article | Journal: Cancer letters | Year: 2012

Matrix metalloproteinases (MMPs) are proteases responsible for remodeling the extracellular matrix (ECM) and enabling spreading and metastasis of tumor cells, a common phenomenon in oral squamous cell carcinomas (OSCC). They are strongly blocked by several inhibitors, among which we must highlight, for their specificity and potency, the endogenous tissue inhibitors of metalloproteinases (TIMP-1, -2, -3 and -4). The goal of this paper is to describe the expression of TIMPs in OSCC, determining their relation with clinical, histological and prognostic factors, delving into OSCC regulation mechanisms and discussing the use of exogenous TIMPs to treat this type of tumors. Expression of TIMPs in OSCC is higher in tumors than in normal tissue, which correlates with an increase of metastatic risk and regional lymph node affectation. Although some metalloproteinases inhibitors (MMIs) have shown promising results in the treatment of these tumors, their use in OSCC has not been widely tested; and although some indirect MMIs, like COX-2 inhibitors, flavonoids and endostatin seem to have beneficial effects on the invasive capacity of OSCC through regulation of MMPs and TIMP levels, routine clinical use has not been accepted yet.

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