RESUMEN
During the last decades, genomic medicine has made it possible to bring the knowledge of molecular genetics to the field of medical consultation. There are several studies that contribute to the diagnosis, the definition of prognoses, as well as the possibility of providing genetic counseling based on accurate scientific data. Advances in genomic sequencing have promoted the reclassification of entities according to an etiological criterion. Such is the case of epileptic encephalopathies, ataxias, dystonias, among many other neurological conditions. Its implementation requires strategies aimed at achieving the best diagnostic yield. This requires a greater understanding of the molecular bases of each of these practices, as well as their scope. They allow reducing the time until a certain diagnosis is made and the possibility, in some cases, of improving the quality of life of those affected with the use of tailored treatments. The objective of this article was to describe current laboratory studies, their scope and emphasize the algorithms for the study of genetic diseases in general, focusing the attention on those specific to neuropediatrics, in order to promote good practices, avoiding confusion, errors, and unnecessary expenditures of money and shortening the so-called "diagnostic odyssey".
Durante las últimas décadas la medicina genómica ha llevado al ámbito de la consulta médica los conocimientos de la genética molecular. Existe un número de estudios que contribuyen en el diagnóstico, la definición de pronósticos y posibilitan un asesoramiento genético basado en datos científicos certeros. En algunas enfermedades, los avances en la secuenciación genómica, ha promovido la reclasificación de entidades según un criterio etiológico, como las encefalopatías epilépticas, las ataxias, las distonías, entre muchas condiciones médicas. Su implementación requiere, por parte de los médicos, de estrategias tendientes a alcanzar el mejor rédito diagnóstico. Es necesario para ello, una mayor comprensión de las bases moleculares de estas prácticas, así como sus alcances. Permiten reducir los tiempos hasta la concreción de un diagnóstico de certeza y la posibilidad, en algunos casos, de mejorar la calidad de vida de los afectados con la utilización de tratamientos a la medida. El objetivo de este artículo fue describir las técnicas de laboratorio actuales, sus alcances y enfatizar los algoritmos de estudio de las enfermedades genéticas, haciendo hincapié en aquellas propias de la neuropediatría, a fin de propiciar las buenas prácticas, evitando confusiones, errores, erogaciones innecesarias de dinero y acortando la llamada "odisea diagnóstica".
Asunto(s)
Pruebas Genéticas , Enfermedades del Sistema Nervioso , Humanos , Asesoramiento Genético , Pruebas Genéticas/métodos , Pruebas Genéticas/normas , Enfermedades del Sistema Nervioso/genética , Enfermedades del Sistema Nervioso/diagnóstico , Guías de Práctica Clínica como AsuntoRESUMEN
BACKGROUND: In this article, we delineate a loosely selected cohort comprising patients with a history of early-onset breast cancer and/or a familial occurrence of cancer. The aim of this study was to gain insights into the presence of breast cancer-related gene variants in a population from a micro-region in southern Brazil, specifically the Metropolitan Region of Curitiba. This area exhibits a highly genetically mixed population, mirroring the general characteristics of the Brazilian people. METHODS: Comprehensive next-generation sequencing (NGS) multigene panel testing was conducted on 12 patients from the region, utilizing three different library preparation methods. RESULTS: Two pathogenic variants and one candidate pathogenic variant were identified: BRCA2 c.8878C>T, p.Gln2960Ter; CHEK2 c.1100del, p.Thr367Metfs15, and BRCA2 c.3482dup, p.Asp1161Glufs3. CONCLUSION: BRCA2 c.3482dup, a novel candidate pathogenic variant, previously unpublished, is reported. The prevalence of pathogenic variants in this small cohort is similar to that described in the literature. All different library preparation methods were equally proficient in enabling the detection of these variants.
Asunto(s)
Proteína BRCA2 , Neoplasias de la Mama , Quinasa de Punto de Control 2 , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Proteína BRCA2/genética , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Quinasa de Punto de Control 2/genética , Brasil , Persona de Mediana Edad , Adulto , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Pruebas Genéticas/métodos , Pruebas Genéticas/normas , Predisposición Genética a la EnfermedadRESUMEN
Exome and genome sequencing (ES/GS) are routinely used for the diagnosis of genetic diseases in developed countries. However, their implementation is limited in countries from Latin America. We aimed to describe the results of GS in patients with suspected rare genetic diseases in Colombia. We studied 501 patients from 22 healthcare sites from January to December 2022. GS was performed in the index cases using dried blood spots on filtercards. Ancestry analysis was performed under iAdmix. Multiomic testing was performed when needed (biomarker, enzymatic activity, RNA-seq). All tests were performed at an accredited genetic laboratory. Ethnicity prediction data confirmed that 401 patients (80%) were mainly of Amerindian origin. A genetic diagnosis was established for 142 patients with a 28.3% diagnostic yield. The highest diagnostic yield was achieved for pathologies with a metabolic component and syndromic disorders (p < 0.001). Young children had a median of 1 year of diagnostic odyssey, while the median time for adults was significantly longer (15 years). Patients with genetic syndromes have spent more than 75% of their life without a diagnosis, while for patients with neurologic and neuromuscular diseases, the time of the diagnostic odyssey tended to decrease with age. Previous testing, specifically karyotyping or chromosomal microarray were significantly associated with a longer time to reach a definitive diagnosis (p < 0.01). Furthermore, one out of five patients that had an ES before could be diagnosed by GS. The Colombian genome project is the first Latin American study reporting the experience of systematic use of diagnostic GS in rare diseases.
Asunto(s)
Enfermedades Raras , Secuenciación Completa del Genoma , Humanos , Colombia , Enfermedades Raras/genética , Enfermedades Raras/diagnóstico , Adulto , Masculino , Femenino , Niño , Secuenciación Completa del Genoma/normas , Adolescente , Preescolar , Pruebas Genéticas/métodos , Pruebas Genéticas/normas , Persona de Mediana Edad , LactanteRESUMEN
Inherited bleeding disorders (IBDs) are the most frequent congenital diseases in the Colombian population; three of them are hemophilia A (HA), hemophilia B (HB), and von Willebrand Disease (VWD). Currently, diagnosis relies on multiple clinical laboratory assays to assign a phenotype. Due to the lack of accessibility to these tests, patients can receive an incomplete diagnosis. In these cases, genetic studies reinforce the clinical diagnosis. The present study characterized the molecular genetic basis of 11 HA, three HB, and five VWD patients by sequencing the F8, F9, or the VWF gene. Twelve variations were found in HA patients, four in HB patients, and 19 in WVD patients. From these variations a total of 25 novel variations were found. Disease-causing variations were used as positive controls for validation of the high-resolution melting (HRM) variant-scanning technique. This approach is a low-cost genetic diagnostic method proposed to be incorporated in developing countries. For the data analysis, we developed an accessible open-source code in Python that improves HRM data analysis with better sensitivity of 95% and without bias when using different HRM equipment and software. Analysis of amplicons with a length greater than 300 bp can be performed by implementing an analysis by denaturation domains.
Asunto(s)
Trastornos de la Coagulación Sanguínea Heredados/diagnóstico , Biología Computacional/métodos , Factor IX/genética , Pruebas Genéticas/métodos , Hemofilia A/genética , Factor de von Willebrand/genética , Trastornos de la Coagulación Sanguínea Heredados/genética , Colombia , Biología Computacional/economía , Biología Computacional/normas , Costos y Análisis de Costo , Factor IX/química , Pruebas Genéticas/economía , Pruebas Genéticas/normas , Hemofilia A/diagnóstico , Humanos , Dominios Proteicos , Sensibilidad y Especificidad , Factor de von Willebrand/químicaRESUMEN
The complete mutational spectrum of dystrophinopathies and limb-girdle muscular dystrophy (LGMD) remains unknown in Mexican population. Seventy-two unrelated Mexican male patients (73% of pediatric age) with clinical suspicion of muscular dystrophy and no evidence of DMD gene deletion on multiplex polymerase chain reaction (mPCR) analysis were analyzed by multiplex ligation-dependent probe amplification (MLPA). Those with a normal result were subjected to Sanger sequencing or to next-generation sequencing for DMD plus 10 selected LGMD-related genes. We achieved a diagnostic genotype in 80.5% (n = 58/72) of patients with predominance of dystrophinopathy-linked genotypes (68%, n = 49/72), followed by autosomal recessive LGMD-related genotypes (types 2A-R1, 2C-R5, 2E-R4, 2D-R3 and 2I-R9; 12.5%, n = 9/72). MLPA showed 4.2% of false-negatives for DMD deletions assessed by mPCR. Among the small DMD variants, 96.5% (n = 28/29) corresponded to null-alleles, most of which (72%) were inherited through a carrier mother. The FKRP p.[Leu276Ile]; [Asn463Asp] genotype is reported for the first time in Mexican patients as being associated with dilated cardiomyopathy. Absence of dysferlinopathies could be related to the small sample size and/or the predominantly pediatric age of patients. The employed strategy seems to be an affordable diagnosis approach for Mexican muscular dystrophy male patients and their families.
Asunto(s)
Distrofina/genética , Pruebas Genéticas/normas , Distrofia Muscular de Duchenne/genética , Mutación , Adolescente , Adulto , Niño , Preescolar , Reacciones Falso Negativas , Pruebas Genéticas/métodos , Genotipo , Humanos , Masculino , México , Reacción en Cadena de la Polimerasa Multiplex/métodos , Reacción en Cadena de la Polimerasa Multiplex/normas , Distrofia Muscular de Duchenne/patología , Pentosiltransferasa/genéticaRESUMEN
BACKGROUND: Germline pathogenic variants in BRCA1 and BRCA2 (BRCA) are the main cause of Hereditary Breast and Ovarian Cancer syndrome (HBOC). METHODS: In this study we evaluated the mutational profile and prevalence of BRCA pathogenic/likely pathogenic variants among probands fulfilling the NCCN HBOC testing criteria. We characterized the clinical profile of these individuals and explored the performance of international testing criteria. RESULTS: A pathogenic/likely pathogenic variant was detected in 19.1% of 418 probands, including seven novel frameshift variants. Variants of uncertain significance were found in 5.7% of individuals. We evaluated 50 testing criteria and mutation probability algorithms. There was a significant odds-ratio (OR) for mutation prediction (p ≤ 0.05) for 25 criteria; 14 of these had p ≤ 0.001. Using a cutoff point of four criteria, the sensitivity is 83.8%, and the specificity is 53.5% for being a carrier. The prevalence of pathogenic/likely pathogenic variants for each criterion ranged from 22.1% to 55.6%, and criteria with the highest ORs were those related to triple-negative breast cancer or ovarian cancer. CONCLUSIONS: This is the largest study of comprehensive BRCA testing among Brazilians to date, and the first to analyze clinical criteria for genetic testing. Several criteria that are not included in the NCCN achieved a higher predictive value. Identification of the most informative criteria for each population will assist in the development of a rational approach to genetic testing, and will enable the prioritization of high-risk individuals as a first step towards offering testing in low-income countries.
Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/genética , Neoplasias Ováricas/genética , Neoplasias de la Mama Triple Negativas/genética , Adulto , Anciano , Brasil , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Femenino , Predisposición Genética a la Enfermedad , Pruebas Genéticas/normas , Síndrome de Cáncer de Mama y Ovario Hereditario , Humanos , Masculino , Persona de Mediana Edad , Mutación , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/patología , Neoplasias de la Mama Triple Negativas/diagnóstico , Neoplasias de la Mama Triple Negativas/epidemiología , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
Catecholaminergic polymorphic ventricular tachycardia is a rare cause of exercise-induced arrhythmia and sudden cardiac death in the pediatric patient. This arrhythmia is difficult to diagnose in the emergency department, given the range of presentations; thus, a familiarity with and high index of suspicion for this pathology are crucial. Furthermore, recognition of the characteristic electrocardiogram findings and knowledge of the management of the symptomatic patient are necessary, given the risk of arrhythmia recurrence and cardiac arrest. In this review, we discuss the presentation, differential diagnosis, and management of catecholaminergic polymorphic ventricular tachycardia for the emergency care provider.
Asunto(s)
Muerte Súbita Cardíaca/etiología , Síncope/diagnóstico , Taquicardia Ventricular/complicaciones , Adolescente , Antiarrítmicos/uso terapéutico , Arritmias Cardíacas/diagnóstico , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/prevención & control , Desfibriladores Implantables , Diagnóstico Diferencial , Electrocardiografía/métodos , Servicio de Urgencia en Hospital , Ejercicio Físico/fisiología , Pruebas Genéticas/normas , Humanos , Masculino , Síncope/etiología , Taquicardia Ventricular/genética , Taquicardia Ventricular/fisiopatología , Taquicardia Ventricular/terapiaRESUMEN
The aim of this review is to describe a series of ten genetic diseases with Mendelian inheritance pattern in people of low- or middle-income countries, which can be easily identified with simple and affordable methods. Recent information shows that although genetic diseases account for more than 10% of infant mortality in such countries, testing, counseling, and treatment of genetic diseases is not a priority. The selection criteria for the genetic tests that are discussed in this review are: i) the frequency of the genetic disease in the general population, ii) the cost and ease of execution, and iii) the report of validated methods in the literature for the diagnosis of these diseases. The goal is to promote diagnosis of genetic diseases at low-cost and with relative ease, thereby enabling appropriate treatments, reducing mortality, and preventing genetic diseases in high-risk families.
Asunto(s)
Enfermedades Genéticas Congénitas/epidemiología , Enfermedades Genéticas Congénitas/genética , Pruebas Genéticas , Países en Desarrollo , Enfermedades Genéticas Congénitas/diagnóstico , Pruebas Genéticas/economía , Pruebas Genéticas/métodos , Pruebas Genéticas/normas , Humanos , Tamizaje Masivo , Vigilancia de la Población , Factores SocioeconómicosRESUMEN
The aim of molecular genetic analysis in families with haemophilia is to identify the causative mutation in an affected male as this provides valuable information for the patient and his relatives. For the patient, mutation identification may highlight inhibitor development risk or discrepancy between different factor VIII assays. For female relatives, knowledge of the familial mutation can facilitate carrier status determination and prenatal diagnosis. Recent advances in understanding mutations responsible for haemophilia and methods for their detection are presented. For reporting of such mutations, participation in external quality assessment ensures that essential patient and mutation details are routinely included and that pertinent information is incorporated in the interpretation.
Asunto(s)
Trastornos de la Coagulación Sanguínea/diagnóstico , Trastornos de la Coagulación Sanguínea/genética , Pruebas Genéticas , Factor IX/genética , Factor VIII/genética , Pruebas Genéticas/métodos , Pruebas Genéticas/normas , Hemofilia A/diagnóstico , Hemofilia A/genética , Hemofilia B/diagnóstico , Hemofilia B/genética , Humanos , MutaciónAsunto(s)
Actitud del Personal de Salud , Pruebas Genéticas/normas , Oncología Médica , Neoplasias/genética , Médicos , Femenino , Humanos , MasculinoRESUMEN
Microsatellite instability (MSI) testing has been advocated for all newly diagnosed colorectal cancer patients. One of the most common tests is composed by a pentaplex panel of mononucleotides markers (NR-27, NR-21, NR-24, BAT-25, and BAT-26), which allows the analysis of MSI in tumors without the need of reference DNA. For that, it is fundamental to establish a quasi-monomorphic variation range (QMVR) for each marker. Herein, we aimed to establish the QMVR in a Brazilian healthy population, to evaluate the feasibility of MSI determination of tumors, without the matching normal DNA. Furthermore, we intend to assess their ancestry using specific ancestry-informative markers (AIMs) and correlate with QMVR. The QMVR was assessed in 214 individuals, through a pentaplex PCR followed by fragment analysis. The ancestry analysis was done by 46 AIMs in a single multiplex PCR followed by capillary electrophoresis. Following QMVR establishment, we observed 23 individuals with alleles outside the QMVR. Importantly, none of them exhibited more than one marker outside the range. Therefore, individuals with instability at ≥2 markers would be accurately classified as MSI. The European ancestry proportion was the most frequent (67.5%), followed by the African (19.6%). The comparison of the individuals with alleles within (n=191) and outside (n=23) the QMVR showed statistical difference in the proportions of European and African alleles, confirming the higher polymorphic nature of African ancestry. In conclusion, the present study reports an accurate methodology to assess MSI status without matched-normal DNA and independently of the ethnicity, even in the highly admixed population of Brazil.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Pruebas Genéticas/métodos , Inestabilidad de Microsatélites , Reacción en Cadena de la Polimerasa Multiplex/métodos , Adulto , Población Negra/genética , Brasil , Células CACO-2 , Femenino , Pruebas Genéticas/normas , Humanos , Masculino , Reacción en Cadena de la Polimerasa Multiplex/normas , Población Blanca/genéticaAsunto(s)
Enfermedad Celíaca/dietoterapia , Enfermedad Celíaca/diagnóstico , Técnicas de Diagnóstico del Sistema Digestivo/normas , Dieta Sin Gluten/normas , Gastroenterología/normas , Salud Global/normas , Sociedades Médicas/normas , Biopsia/normas , Enfermedad Celíaca/epidemiología , Endoscopía Gastrointestinal/normas , Pruebas Genéticas/normas , Humanos , Cooperación del Paciente , Valor Predictivo de las Pruebas , Pruebas Serológicas/normas , Resultado del TratamientoRESUMEN
Genetic diseases and congenital anomalies are the second most common cause of infant mortality in Brazil. In 2009, the Ministry of Health established the National Policy for Integral Attention in Clinical Genetics in the Brazilian Unified National Health System (UNHS). This policy is not yet regulated, and there is a fear that, in the name of the comprehensiveness of health care, genetic testing might be carried out without due care and criteria, increasing costs to the UNHS. Currently, only a small population has access to genetic testing, through teaching hospitals or private health care. The biggest challenge in Brazil, in this area, is to be able to set the right standards and assessment processes about clinical utility, testing priorities, dispersal of resources, and distribution of skilled professionals. Expanding access to users of the Brazilian UNHS will mean mining the technical, social, and ethical aspects about medical genetics services.
Asunto(s)
Anomalías Congénitas/genética , Enfermedades Genéticas Congénitas/genética , Pruebas Genéticas/legislación & jurisprudencia , Pruebas Genéticas/métodos , Animales , Brasil/epidemiología , Anomalías Congénitas/diagnóstico , Anomalías Congénitas/epidemiología , Enfermedades Genéticas Congénitas/diagnóstico , Enfermedades Genéticas Congénitas/epidemiología , Pruebas Genéticas/normas , Pruebas Genéticas/tendenciasRESUMEN
INTRODUCTION: Thrombotic complications are a main concern in patients with myeloproliferative neoplasms. Recently, a gain-of-function mutation of the gene encoding the JAK2 tyrosine kinase that results in a valine-to-phenylalanine substitution at position 617 (V617F) has been described. Since the description of the JAK2-V617F mutation and its finding in patients with splanchnic vein thrombosis without an overt myeloproliferative neoplasm, many groups have studied the prevalence of this mutation in patients with unexplained venous and arterial thrombosis. METHODS: A literature search was made using the key words thrombosis, JAK2V617F mutation, myeloproliferative neoplasms, cerebral vein thrombosis and splanchnic vein thrombosis. RESULTS: JAK2V617F is frequent in patients with splanchnic vein thrombosis, but is rare in patients with venous thrombosis at other locations or with arterial thrombosis. CONCLUSION: Routine testing for JAK2V617F is not currently recommended for patients with unexplained thromboses, except for those with splanchnic vein thrombosis. In patients with cerebral vein thrombosis, the value of testing for JAK2V617F mutation is yet to be established.
Asunto(s)
Pruebas Genéticas , Janus Quinasa 2/genética , Mutación , Trombosis/genética , Venas Cerebrales/patología , Predisposición Genética a la Enfermedad , Pruebas Genéticas/normas , Humanos , Venas Mesentéricas/patología , Trastornos Mieloproliferativos/complicaciones , Trastornos Mieloproliferativos/genética , Trombosis/etiologíaRESUMEN
We report the use of a genetic test for therapeutic decision making in a case of primary hyperparathyroidism associated with Cushing's disease (CD). A 20-year-old woman was evaluated for gradual weight gain, asthenia, muscle pain, and hypertension. Biochemical and radiologic tests confirmed CD and she underwent transsphenoidal surgery. Immunohistochemistry of the microadenoma was positive for adrenocorticotropic hormone (ACTH). On follow-up, hypercalcemia with high parathyroid hormone (PTH) levels was detected, associated with nephrolithiasis and low bone mineral density in the spine and hip. Parathyroid scintigraphy showed tracer uptake in the inferior region of the left thyroid lobe, and cervical ultrasound showed a heterogeneous nodule in the same area, suggestive of a parathyroid adenoma (PA). Genetic testing detected mutation in the MEN 1 gene and total parathyroidectomy with the implantation of a fragment of one gland in the forearm was performed. Pathology showed a PA and 3 normal parathyroid glands, without hyperplasia, despite the diagnosis of MEN 1. This case illustrates the role of genetic testing in defining the therapeutic approach for sporadic MEN 1.
Relatamos o uso de teste genético para decisão terapêutica em um caso de hiperparatireoidismo primário associado com doença de Cushing (DC). Uma jovem de 20 anos foi avaliada por ganho de peso gradual, astenia, mialgias e hipertensão. Os exames complementares confirmaram DC e ela foi submetida à cirurgia transesfenoidal. A análise imuno-histoquímica do microadenoma foi positiva para hormônio adrenocorticotrófico (ACTH). No seguimento, a paciente apresentou hipercalcemia com níveis elevados de hormônio de paratireoide (PTH), nefrolitíase e densidade mineral óssea baixa em coluna e fêmur. A cintilografia de paratireoide mostrou captação do traçador em região inferior do lobo esquerdo da tireoide e a ecografia cervical revelou nódulo heterogêneo na mesma área, sugestivo de adenoma da paratireoide (AP). O teste genético detectou mutação no gene MEN 1 e ela foi submetida à paratireoidectomia total com implante de fragmento de uma das glândulas no antebraço. A patologia confirmou AP e as outras três glândulas normais, sem hiperplasia, apesar do diagnóstico de MEN 1. Esse caso ilustra a importância do teste genético para definir a abordagem terapêutica em um caso esporádico de MEN 1.
Asunto(s)
Femenino , Humanos , Adulto Joven , Adenoma/genética , Pruebas Genéticas/normas , Hiperparatiroidismo Primario/genética , Neoplasia Endocrina Múltiple Tipo 1/genética , Neoplasias de las Paratiroides/genética , Toma de Decisiones , Mutación , Neoplasia Endocrina Múltiple Tipo 1/cirugía , Neoplasias de las Paratiroides , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/genética , Proteínas Proto-Oncogénicas/genéticaRESUMEN
The knowledge of the human genome has led to an explosion of available genetic tests for clinical use. The methodologies used in these tests vary widely, allowing the study from chromosomes to the analysis of a single nucleotide. Prior to its use in the clinical setting, these tests should have an evaluation that includes analytical and clinical validation and determination of the clinical utility, as any other tests, including requirements for quality assurance. Recently, the CDC (Centers for Disease Control and Prevention, USA) published a guideline for Good Laboratory Practices for Molecular Genetic Testing for Heritable Diseases and Conditions, covering the pre-analytical, analytical and post-analytical phases of the tests. The document covers the importance of proper selection of tests, the availability of information on the performance of the techniques used, the quality control practices, the training of personnel involved and the report of results, to allow the adequate interpretation, including sensitivity and specificity. Considering that recent advances in genetics have changed and will continue to affect clinical practice, genetic tests must meet quality and safety requirements to enable optimal use of them.
Asunto(s)
Pruebas Genéticas/métodos , Pruebas Genéticas/normas , Humanos , Guías de Práctica Clínica como AsuntoRESUMEN
The knowledge of the human genome has led to an explosion of available genetic tests for clinical use. The methodologies used in these tests vary widely, allowing the study from chromosomes to the analysis of a single nucleotide. Prior to its use in the clinical setting, these tests should have an evaluation that includes analytical and clinical validation and determination of the clinical utility, as any other tests, including requirements for quality assurance. Recently, the CDC (Centers for Disease Control and Prevention, USA) published a guideline for Good Laboratory Practices for Molecular Genetic Testing for Heritable Diseases and Conditions, covering the pre-analytical, analytical and post-analytical phases of the tests. The document covers the importance of proper selection of tests, the availability of information on the performance of the techniques used, the quality control practices, the training of personnel involved and the report of results, to allow the adequate interpretation, including sensitivity and specificity. Considering that recent advances in genetics have changed and will continue to affect clinical practice, genetic tests must meet quality and safety requirements to enable optimal use of them.
El conocimiento del genoma humano ha dado lugar a un aumento explosivo de los test genéticos disponibles para uso clínico. Las metodologías utilizadas en este tipo de tests son muy variadas, permitiendo desde el estudio de los cromosomas hasta el análisis de una base nucleotídica. Previo a su utilización en el ámbito clínico, estos tests deben tener una evaluación que incluya su validación analítica y clínica y determinación de la utilidad clínica, además de cumplir, como cualquier otro examen, con requisitos para el aseguramiento de la calidad. Recientemente, el CDC (Centersfor Disease Control and Prevention, EE. UU) hapublicado recomendaciones para las buenas prácticas de laboratorio de tests moleculares que se utilizan para el diagnóstico de enfermedades genéticas, que abarcan la fase pre- analítica, analítica y post-analítica. Dentro de éstas destacan: la importancia de la selección adecuada de los tests, la disponibilidad de la información sobre el desempeño de las técnicas utilizadas, las prácticas de control de calidad, la capacitación del personal involucrado y la elaboración de un informe de resultados que permita al clínico interpretarlos adecuadamente, incluyendo sensibilidad y especificidad. Tomando en cuenta que los recientes avances en genética han modificado y seguirán modificando la práctica clínica, los test genéticos deben cumplir con las exigencias de calidady seguridad que permitan su uso óptimo.