Construction and practice of cancer genetic clinic / 中华医学遗传学杂志

OBJECTIVE@#To explore the effect and precautions of setting up a genetic clinic for hereditary colorectal cancers.@*METHODS@#To collect the information of the patients who received genetic screening and genetic counseling at our hospital from January 2016 to June 2018, and analyze the role of family history collection and follow-up management.@*RESULTS@#The detection rate of family history of tumors has increased by 13.6%. Follow up management was carried out in 156 families with hereditary colorectal cancer confirmed by detection of germline mutations. Five cases of early colorectal cancers and 12 cases of adenomatous polyps were detected and treated.@*CONCLUSION@#To set up genetic clinic is helpful to standardize the management of high-risk population, and attention should be paid to the role of family history collection and follow-up management.

Development and Characterization of Reference Materials for Genetic Testing: Focus on Public Partnerships

Characterized reference materials (RMs) are needed for clinical laboratory test development and validation, quality control procedures, and proficiency testing to assure their quality. In this article, we review the development and characterization of RMs for clinical molecular genetic tests. We describe various types of RMs and how to access and utilize them, especially focusing on the Genetic Testing Reference Materials Coordination Program (Get-RM) and the Genome in a Bottle (GIAB) Consortium. This review also reinforces the need for collaborative efforts in the clinical genetic testing community to develop additional RMs.

Application of genetic testing to define the surgical approach in a sporadic case of multiple endocrine neoplasia type 1 / Aplicação de teste genético para definição da conduta cirúrgica num caso esporádico de neoplasia endócrina múltipla do tipo 1

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.

Tests genéticos: Definición, métodos, validación y utilidad clínica / Genetic tests: Definition, methods, validity and clinical utility

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.

Premarital genetic investigations: effect of genetic counselling

Over a period of 2 years, 86 couples [172 cases] were referred to the genetics clinic of the National Research Centre for premarital genetic counselling. About 73.25% had a family history of different genetic disorders. Consanguinity was found in 86.04%. Genetic investigations revealed chromosomal abnormalities in 26 cases [15.11%]; 23 cases [13.37%] had other abnormal results. After genetic counselling, postconceptional follow-up was carried out for 30 couples; 10 of them required amniocentesis that showed abnormal fetuses in 2 mothers. Other couples had normal offspring. We conclude that premarital genetic counselling is of great use in the detection of genetic disorders and is an essential step in changing attitudes towards premarital testing and reducing consanguineous marriage