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5 results on '"Secuenciación del exoma completo"'

1. Editorial: Epidemiology and Genetics of Vestibular Disorders

Author

Jose A. Lopez-Escamez, Alan G. Cheng, Eva Grill, Tien-Chen Liu, [Lopez-Escamez,JA] Otology and Neurotology Group CTS495, Department of Genomic Medicine, GENYO - Centre for Genomics and Oncological Research - Pfizer/University of Granada/Junta de Andalucía, Parque Tecnologico de la Salud (PTS), Granada, Spain. [Lopez-Escamez,JA] Department of Otolaryngology, Instituto de Investigación Biosanitaria, ibs.GRANADA, Hospital Universitario Virgen de las Nieves, Granada, Spain. [Lopez-Escamez,JA] Division of Otolaryngology, Department of Surgery, Universidad de Granada, Granada, Spain. [Lopez-Escamez,JA] Sensorineural Pathology Programme, Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Madrid, Spain. [Cheng,AG] Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, United States. [Grill,E] Institute for Medical Information Processing, Biometrics and Epidemiology, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany. [Grill,E] German Center for Vertigo and Balance Disorders, University Hospital Munich, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany. [Grill,E] Munich Centre of Health Sciences, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany. [Liu,TC] Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan., and JL-E received research support from the Instituto de Salud Carlos III, European Regional Funds (Grant PI20/1126), Andalusian Family & Health Department (Grant PI027/2020), and the European Union (Horizon 2020, Grant Agreement 848261).

Subjects
Exome sequencing, Familial aggregation, Herencia, medicine.medical_specialty, Vestibular disorders, Trastornos migrañosos, vestibular migraine, heritability, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Cluster Analysis [Medical Subject Headings], Enfermedades del nervio vestibulococlear, Vestibular migraine, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Neurologic Manifestations::Dyskinesias::Ataxia [Medical Subject Headings], MENIERE DISEASE, Heritability, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], RNA seq, Epidemiology, medicine, Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Headache Disorders::Headache Disorders, Primary::Migraine Disorders [Medical Subject Headings], RC346-429, Diseases::Otorhinolaryngologic Diseases::Ear Diseases::Labyrinth Diseases::Vestibular Diseases [Medical Subject Headings], Diseases::Cardiovascular Diseases [Medical Subject Headings], Genetics, Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebellar Diseases [Medical Subject Headings], Secuenciación del exoma completo, business.industry, Enfermedad de Meniere, Disciplines and Occupations::Health Occupations::Medicine::Neurology::Neurotology [Medical Subject Headings], Family aggregation, Diseases::Nervous System Diseases::Autonomic Nervous System Diseases::Primary Dysautonomias::Orthostatic Intolerance::Hypotension, Orthostatic [Medical Subject Headings], Health Care::Health Services Administration::Patient Care Management::Comprehensive Health Care::Primary Health Care [Medical Subject Headings], familial aggregation, Neurology, Meniere disease, Persons::Persons::Occupational Groups::Health Personnel::Physicians::Physicians, Primary Care [Medical Subject Headings], Migraine disorders, Neurology (clinical), Neurology. Diseases of the nervous system, Anatomy::Sense Organs::Ear::Ear, Inner::Vestibule, Labyrinth::Saccule and Utricle::Acoustic Maculae::Otolithic Membrane [Medical Subject Headings], business, exome sequencing
Abstract

Yes

Published
2021

2. Wiedemann-Steiner syndrome with a novel pathogenic variant in KMT2A: a case report

Author

Diana Ramirez-Montaño and Harry Pachajoa

Subjects
Hipertricosis, Hypertrichosis, Secuenciación del Exoma completo, Case Report, Short stature, whole exome sequencing, Frameshift mutation, histone methyltransferases, 03 medical and health sciences, Genotype-phenotype distinction, Medicine, Exome sequencing, 030304 developmental biology, Genetics, 0303 health sciences, business.industry, Genetic heterogeneity, 030305 genetics & heredity, Genetic disorder, Mutación frameshift, Metiltransferasa de histonas, General Medicine, medicine.disease, hypertrichosis, Discapacidad intelectual, Wiedemann-Steiner syndrome, intellectual disability, Reporte De Caso, medicine.symptom, business
Abstract

Case Description: We report the case of a one-year-old girl who was diagnosed with Wiedemann-Steiner Syndrome based on the identification of a novel de novo frameshift mutation in the KMT2A gene by whole exome sequencing and supported by her clinical features. Clinical Findings: KMT2A mutations cause Wiedemann-Steiner Syndrome, a very rare genetic disorder characterized by congenital hypertrichosis, short stature, intellectual disability, and distinct facial features. Treatment and Outcome: Whole exome sequencing identified a novel frameshift variant: c. 4177dupA (p.Ile1393Asnfs * 14) in KMT2A ; this change generates an alteration of the specific binding to non-methylated CpG motifs of the DNA to the protein. The genotype and phenotype of the patient were compared with those of earlier reported patients in the literature. Clinical Relevance: In diseases with low frequency, it is necessary to establish a genotype-phenotype correlation that allows the establishment of therapeutic and follow-up goals. The phenotype comparation with other reported cases did not show differences attributable to sex or age among patients with Wiedemann-Steiner Syndrome. Whole exome sequencing allows identifying causality in conditions with high clinical and genetic heterogeneity like hypertrichosis.

Published
2019

3. Comprehensive genomic profile of heterogeneous long follow-up triple-negative breast cancer and its clinical characteristics shows DNA repair deficiency has better prognostic

Author

Enrique Bargallo-Rocha, Luis I. Terrazas, Clara Díaz-Velásquez, Fernando Vallejo-Lecuona, Fany Iris Porras Reyes, Aldo de la Cruz-Montoya, Javier Oliver, Javier César Mejía-Gómez, Sandra Perdomo, Víctor Pérez-Sánchez, Héctor Martínez Gregorio, Paula Cabrera-Galeana, Cecilia Frecha, Maritza Ramos-Ramírez, Yolanda I. Chirino, Rosalía Quezada-Urban, Felipe Vaca-Paniagua, Luis A. Herrera, Ernesto Rojas-Jiménez, Maybelline Robles-Estrada, Héctor Maldonado-Martinez, [Rojas-Jiménez,E, Díaz-Velásquez,C, Quezada-Urban,R, Martínez Gregorio,H, Vallejo-Lecuona,F, Terrazas,LI, Vaca-Paniagua,F] Laboratorio Nacional en Salud, Diagnóstico Molecular y Efecto Ambiental en Enfermedades Crónico-Degenerativas, Facultad de Estudios Superiores Iztacala, Tlalnepantla, Estado de México, Mexico. [Rojas-Jiménez,E, de la Cruz-Montoya,A, Chirino,YI, Vaca-Paniagua,F] Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, UNAM, Tlalnepantla, Estado de México, Mexico. [Mejía-Gómez,JC] Division of Breast Cancer, Department of Medical Oncology, Mt. Sinai Hospital, University of Toronto, Toronto, ON, Canada. [Quezada-Urban,R] Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia. [Quezada-Urban,R] Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. [Porras Reyes,FI, Pérez-Sánchez,VM, Maldonado-Martínez,HA, Bargalló-Rocha,E, Cabrera-Galeana,P, Ramos-Ramírez,M, Alonso Herrera,L, Vaca-Paniagua,F] Instituto Nacional de Cancerología, CDMX, Mexico. [Robles-Estrada,M] Hospital General de Pachuca SSA, Pachuca, Mexico. [Alonso Herrera,L] Instituto Nacional de Medicina Genómica, CDMX, Mexico. [Alonso Herrera,L] Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas-Instituto Nacional de Cancerología, CDMX, Mexico. [Oliver,J] Medical Oncology Service, Hospitales Universitarios Regional y Virgen de la Victoria, Institute of Biomedical Research in Malaga, CIMES, University of Málaga, Málaga, Spain. [Frecha,C] Unidad de Producción Celular del Hospital Regional Universitario de Málaga—IBIMA—Málaga, Málaga, Spain. [Perdomo,S] Instituto de Nutrición, Genética y Metabolismo, Facultad de Medicina, Universidad El Bosque, Bogotá, Colombia. [Perdomo,S] International Agency for Research on Cancer, World Health Organization, Lyon, France., This study was funded by grants from UNAM PAPIIT IN219217 and CONACyT Fondo Sectorial 272573., and Perdomo Lara, Sandra Janneth [0000-0002-4429-3760]

Subjects
0301 basic medicine, Oncology, Terapéutica, Triple Negative Breast Neoplasms, Kaplan-Meier Estimate, whole exome sequencing, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::DNA Repair-Deficiency Disorders [Medical Subject Headings], somatic mutation, Genetics (clinical), Triple-negative breast cancer, Exome sequencing, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], education.field_of_study, biology, treatment, Middle Aged, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms [Medical Subject Headings], 030220 oncology & carcinogenesis, Neoplasias de la mama, triple-negative breast cancer, WES, Female, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA [Medical Subject Headings], Adult, medicine.medical_specialty, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings], lcsh:QH426-470, DNA repair, Population, Mutational signatures, mutational signatures, Article, 03 medical and health sciences, Breast cancer, Germline mutation, Lymphocytes, Tumor-Infiltrating, Internal medicine, Exome Sequencing, Genetics, medicine, PTEN, Humans, education, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, Secuenciación del exoma completo, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Survival Analysis::Kaplan-Meier Estimate [Medical Subject Headings], Somatic mutation, México, Whole exome sequencing, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Neoplasias de la mama triple negativas, medicine.disease, DNA Repair-Deficiency Disorders, Treatment, lcsh:Genetics, 030104 developmental biology, Geographical Locations::Geographic Locations::Americas::North America::Mexico [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Genomic Profile, Mutation, biology.protein, Anatomy::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Lymphocytes, Tumor-Infiltrating [Medical Subject Headings]
Abstract

Triple-negative breast cancer (TNBC) presents a marked diversity at the molecular level, which promotes a clinical heterogeneity that further complicates treatment. We performed a detailed whole exome sequencing profile of 29 Mexican patients with long follow-up TNBC to identify genomic alterations associated with overall survival (OS), disease-free survival (DFS), and pathologic complete response (PCR), with the aim to define their role as molecular predictive factors of treatment response and prognosis. We detected 31 driver genes with pathogenic mutations in TP53 (53%), BRCA1/2 (27%), CDKN1B (9%), PIK3CA (9%), and PTEN (9%), and 16 operative mutational signatures. Moreover, tumors with mutations in BRCA1/2 showed a trend of sensitivity to platinum salts. We found an association between deficiency in DNA repair and surveillance genes and DFS. Across all analyzed tumors we consistently found a heterogeneous molecular complexity in terms of allelic composition and operative mutational processes, which hampered the definition of molecular traits with clinical utility. This work contributes to the elucidation of the global molecular alterations of TNBC by providing accurate genomic data that may help forthcoming studies to improve treatment and survival. This is the first study that integrates genomic alterations with a long follow-up of clinical variables in a Latin American population that is an underrepresented ethnicity in most of the genomic studies.

Published
2020

4. Whole-exome sequencing of 81 individuals from 27 multiply affected bipolar disorder families

Author

Fermín Mayoral, Fabio Rivas, Jesus Haro González, Franziska Degenhardt, Julian Hecker, Fermin Perez Perez, Marcella Rietschel, Michael Bauer, Margot Albus, Markus M. Nöthen, Sascha B. Fischer, Susana Gil Flores, Francisco del Río Noriega, Mehdi Pirooznia, Stefan Herms, Jana Strohmaier, Stephanie H. Witt, Fernando S. Goes, Margitta Borrmann-Hassenbach, Anna Maaser-Hecker, Sugirthan Sivalingam, Sven Cichon, Lorena M. Schenk, Georg Auburger, Andreas Reif, Fabian Streit, María González, Francisco J. Cabaleiro Fabeiro, Peter Nürnberg, Jose Guzman-Parra, Andreas J. Forstner, Holger Thiele, Guillermo Orozco Diaz, Andrea Pfennig, Céline S. Reinbold, Johannes Schumacher, Per Hoffmann, [Forstner,AJ, Schumacher,J] Centre for Human Genetics, University of Marburg, Marburg, Germany. [Forstner,AJ, Schenk,LM, Maaser-Hecker,A, Sivalingam,S, Degenhardt,F, Schumacher,J, Herms,S, Hoffmann,P, Nöthen,MM, Cichon,S] Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany. [Forstner,AJ, Fischer,SB, Reinbold,CS, Cichon,S] Department of Biomedicine, University of Basel, Basel, Switzerland. [Forstner,AJ] Department of Psychiatry (UPK), University of Basel, Basel, Switzerland. [Fischer,SB, Cichon,S] Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland. [Strohmaier,J, Streit,F, Witt,SH, Rietschel,M] Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. [Strohmaier,J] SRH University Heidelberg, Academy for Psychotherapy, Heidelberg, Germany. [Reinbold,CS] Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo, Oslo, Norway. [Hecker,J] Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. [Thiele,H, Nürnberg,P] Cologne Center for Genomics, University of Cologne, Cologne, Germany. [Guzman-Parra,J, González,MJ] Department of Mental Health, University Regional Hospital of Málaga, Institute of Biomedicine of Málaga (IBIMA), Málaga, Spain. [Orozco Diaz,G] Unidad de Gestión Clínica del Dispositivo de Cuidados Críticos y Urgencias del Distrito Sanitario Málaga - Coin- Gudalhorce, Málaga, Spain. [Auburger,G] Experimental Neurology, Department of Neurology, Goethe University Hospital, Frankfurt am Main, Germany. [Albus,M, Borrmann-Hassenbach,M]Isar Amper Klinikum München Ost, kbo, Haar, Germany. [Gil Flores,S] Department of Mental Health, University Hospital of Reina Sofia, Cordoba, Spain. [Cabaleiro Fabeiro,FJ] Department of Mental Health, Hospital of Jaén, Jaén, Spain. [del Río Noriega,F] Department of Mental Health, Hospital of Jerez de la Frontera, Jerez de la Frontera, Spain. [Perez Perez,F] Department of Mental Health, Hospital of Puerto Real, Cádiz, Spain. [Haro González,J] Department of Mental Health, Hospital Punta de Europa, Algeciras, Spain. [Rivas,F, Mayoral,F] Department of Psychiatry, Carlos Haya Regional University Hospital, Malaga, Spain. [Bauer,M, Pfennig,A] Department of Psychiatry and Psychotherapy, Medical Faculty, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. [Reif,A] Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt am Main, Frankfurt am Main, Germany. [Hoffmann,P, Cichon,S] Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, Jülich, Germany. [Pirooznia,M, Goes,FS] Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA, The study was supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under the auspices of the e:Med Programme (grant 01ZX1314A/01ZX1614A to M.M.N. Forstner et al. Translational Psychiatry (2020) 10:57 Page 8 of 10 and S.C., grant 01ZX1314G/01ZX1614G to M.R.) and through ERA-NET NEURON, 'SynSchiz—Linking synaptic dysfunction to disease mechanisms in schizophrenia—a multilevel investigation' (01EW1810 to MR). The study was also supported by the German Research Foundation (DFG, grant FOR2107, RI908/11-1 and RI908/11–2 to M.R., and NO246/10-1 and NO 246/10-2 to M.M.N.), and the Swiss National Science Foundation (SNSF, grant 156791 to S.C.). M.M.N. is a member of the DFG-funded Excellence-Cluster ImmunoSensation.

Subjects
Candidate gene, Bipolar Disorder, Psychiatry and Psychology::Mental Disorders::Mood Disorders::Affective Disorders, Psychotic::Bipolar Disorder [Medical Subject Headings], Neuropsiquiatría, Disease, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Germany, Exome, Exome sequencing, Genetics, 0303 health sciences, Trastorno bipolar, Predisposición genética a la enfermedad, Neuropsychiatry, Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to Disease [Medical Subject Headings], 3. Good health, Pedigree, Psychiatry and Mental health, Schizophrenia, Phenomena and Processes::Genetic Phenomena::Inheritance Patterns::Penetrance [Medical Subject Headings], Psychiatry and Psychology::Mental Disorders::Mental Disorders Diagnosed in Childhood::Child Development Disorders, Pervasive::Autistic Disorder [Medical Subject Headings], Biology, Molecular neuroscience, Article, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Exome [Medical Subject Headings], lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, Exome Sequencing, medicine, Psychiatry and Psychology::Mental Disorders::Schizophrenia and Disorders with Psychotic Features::Schizophrenia [Medical Subject Headings], Humans, Genetic Predisposition to Disease, Bipolar disorder, ddc:610, Allele, Gene, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, 030304 developmental biology, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Secuenciación del exoma completo, Whole exome sequencing, Anatomy::Nervous System::Central Nervous System::Brain [Medical Subject Headings], medicine.disease, Geographical Locations::Geographic Locations::Europe::Germany [Medical Subject Headings], Autism, 030217 neurology & neurosurgery, RGS Proteins
Abstract

Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of depression and mania. Research suggests that the cumulative impact of common alleles explains 25–38% of phenotypic variance, and that rare variants may contribute to BD susceptibility. To identify rare, high-penetrance susceptibility variants for BD, whole-exome sequencing (WES) was performed in three affected individuals from each of 27 multiply affected families from Spain and Germany. WES identified 378 rare, non-synonymous, and potentially functional variants. These spanned 368 genes, and were carried by all three affected members in at least one family. Eight of the 368 genes harbored rare variants that were implicated in at least two independent families. In an extended segregation analysis involving additional family members, five of these eight genes harbored variants showing full or nearly full cosegregation with BD. These included the brain-expressed genes RGS12 and NCKAP5, which were considered the most promising BD candidates on the basis of independent evidence. Gene enrichment analysis for all 368 genes revealed significant enrichment for four pathways, including genes reported in de novo studies of autism (padj padj = 0.015). These results suggest a possible genetic overlap with BD for autism and schizophrenia at the rare-sequence-variant level. The present study implicates novel candidate genes for BD development, and may contribute to an improved understanding of the biological basis of this common and often devastating disease.

Published
2020

5. Novel genes and mutations in patients affected by recurrent pregnancy loss

Author

Carlos F. Suárez, Eric Mercier, Manuel A. Patarroyo, Michiko Fukuda, Daniel Vaiman, Jean-Christophe Gris, Paula Quintero-Ronderos, Ronald Gonzalez, Paul Laissue, Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), National Institute of Advanced Industrial Science and Technology (AIST), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Université Montpellier 1 (UM1), and Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes)

Subjects
Caucásico, Gene Mutation, Secondary, Gene mutation, Pathology and Laboratory Medicine, Gene, Biochemistry, Models, Pregnancy, Fgfr2 Gene, Proteína Mmp1, Thbd Gene, Modificación de ADN, Genetic Stability, Exome sequencing, Clinical Article, Gen Col6A3, Thrombin, High-Throughput Nucleotide Sequencing, Gen F5, Genomics, Col6A3 Gene, Mmp1 Gene, Secuenciación de alto rendimiento, Fibrinogen Alphac, Factor V Deficiency, Ncoa1 Gene, Protein Structure, Genotype, Tro Gene, Adamts1 Gene, Variación genética, Amn gen, Creer gen, Gen Flt1, 03 medical and health sciences, Protein Domains, Gen Mmp9, Enfermedades del aparato genital, Gen Ncoa1, Genetics, Teoría cuántica, Molecular Biology Assays and Analysis Techniques, lcsh:R, Abortion, Biology and Life Sciences, Computational Biology, Proteins, Gen Mmp1, Enfermedades, Fga Gene, Peptide Fragments, Secuenciación de próxima generación, Epas1 Gene, 030104 developmental biology, Quantum Theory, lcsh:Q, Gen Bmp7, Genotipo, Estructura de la proteína, Models, Molecular, Etiology, La expresión génica, Gene Expression, lcsh:Medicine, Bmp7 Gene, Whole Exome Sequencing, Database and Informatics Methods, Gen Fgfr2, Gen Thbd, Medicine and Health Sciences, Gen Cdh11, Multidisciplinary, Gen, Lifr Gene, Deficiencia de Factor V, Deletion Mutation, Phenotype, Cr1 Gene, Función del gen, Factor Xa, Amino Acid Analysis, Thermodynamics, Gen Adams1, Matrix Metalloproteinase 1, Transcriptome Analysis, Adult, Amn Gene, Mmp1 Protein, Gen Ido2, Protein Domain, Secundario, Aborto Recurrente, Pathophysiology, Variabilidad genética, medicine, Fragmento de péptido, Gen Traf3Ip1, Mutación genética, Molecular Model, Genome Analysis, Metabolism, Aborto, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Biología, Disease, Aborto Habitual, El embarazo, 0302 clinical medicine, Fisiopatología, DNA sequencing, Infertilidad, lcsh:Science, Exome, Mutation, 030219 obstetrics & reproductive medicine, Química, Tlr3 Gene, Estromelisina 2, Dominio de proteínas, 3. Good health, Genetic Variability, Fenotipo, Modelo molecular, Human, Next-Generation Sequencing, Abortion, Habitual, Bioinformatics, Secuenciación de nucleótidos de alto rendimiento, Gen Tlr3, Código genético, Gen Tnc, Humans, Protein Interaction Domains and Motifs, Humano, Biology, Secuenciación del exoma completo, Termodinámica, High Throughput Sequencing, Factor V, Molecular, Genetic Variation, Cdh11 Gene, medicine.disease, Habitual, Human genetics, Molecular biology techniques, Sanger Sequencing, Ido2 Gene, Cdh1 Gene, Estabilidad Genética, 0301 basic medicine, Molecular biology, Next Generation Sequencing, Mmp9 Gene, Dna Modification, Estructura secundaria de proteínas, medicine.disease_cause, Protein Structure, Secondary, Fibrinógeno Alphac, Sequencing techniques, Peptide Fragment, Flt1 Gene, Exoma, Fibrinógeno, Protein Secondary Structure, Artículo Clínico, Metabolismo, Dominios y motivos de interacción de proteínas, Traf3Ip1 Gene, Gen lifr, Matriz metaloproteinasa 1, Bioinformática, Protein Interaction Domains And Motifs, Chemistry, Genetic Code, Biología Computacional, Female, Research Article, Fragmentos de péptidos, Gene Sequence, F5 Gene, Gen Cr1, Caucasian, Research and Analysis Methods, Gen Cdh1, Matrix Metalloproteinase 10, Secuencia de genes, Secuenciación de Sangre, Mutación, Gen Fga, Modelos, Fibrinogen, Human Genetics, Reproducción, Genética, Gen Epas1, Recurrent Abortion, Gene Function, Stromelysin 2
Abstract

Recurrent pregnancy loss is a frequently occurring human infertility-related disease affecting ~1% of women. It has been estimated that the cause remains unexplained in >50% cases which strongly suggests that genetic factors may contribute towards the phenotype. Concerning its molecular aetiology numerous studies have had limited success in identifying the disease’s genetic causes. This might have been due to the fact that hundreds of genes are involved in each physiological step necessary for guaranteeing reproductive success in mammals. In such scenario, next generation sequencing provides a potentially interesting tool for research into recurrent pregnancy loss causative mutations. The present study involved whole-exome sequencing and an innovative bioinformatics analysis, for the first time, in 49 unrelated women affected by recurrent pregnancy loss. We identified 27 coding variants (22 genes) potentially related to the phenotype (41% of patients). The affected genes, which were enriched by potentially deleterious sequence variants, belonged to distinct molecular cascades playing key roles in implantation/pregnancy biology. Using a quantum chemical approach method we established that mutations in MMP-10 and FGA proteins led to substantial energetic modifications suggesting an impact on their functions and/or stability. The next generation sequencing and bioinformatics approaches presented here represent an efficient way to find mutations, having potentially moderate/strong functional effects, associated with recurrent pregnancy loss aetiology. We consider that some of these variants (and genes) represent probable future biomarkers for recurrent pregnancy loss. © 2017 Quintero-Ronderos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Published
2017

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