Diagnosis of hereditary diseases: full guide
Hereditary diseases due to genetic mutations are a serious healthcare problem. Early and accurate diagnostics is crucial for effective treatment, prevention of complications and family planning. This comprehensive guide covers a wide range of methods for the diagnosis of hereditary diseases, from traditional clinical assessments to advanced genomic technologies, and also discusses ethical aspects and the future of genetic diagnostics.
I. Fundamentals of hereditary diseases and genetics
Before delving into diagnostic methods, it is necessary to understand the basic principles of heredity and genetic pathology.
- Genes and chromosomes: DNA, bearing genetic information, is organized in genes that are located on chromosomes. A person receives one copy of each chromosome from each parent.
- Mutations: Changes in the DNA sequence, called mutations, can lead to a violation of the gene function and, therefore, to the development of a hereditary disease. Mutations can be spontaneous or inherited.
- Types of heredity:
- Autosomal dominant: To manifest the disease, one copy of the mutant gene is enough.
- Autosoma-RESPECTIVE: To manifest the disease, the presence of two copies of the mutant gene is necessary. Motors of one copy are usually healthy.
- X-scented dominant: The mutant gene is located on the X chromosome, and one copy is enough to manifest the disease in women and men.
- X-scented recessive: The mutant gene is located on the X chromosome, and the disease is usually manifested in men (who have only one X chromosome) and in women only in the presence of two copies of the mutant gene.
- Mitochondrial: Diseases caused by mutations in mitochondrial DNA are transmitted only from the mother.
- Genetic heterogeneity: The same disease can be caused by mutations in various genes (genetic heterogeneity) or various mutations in the same gene (allele heterogeneity).
- Penetrance and expressiveness:
- Penetrance: The probability that the carrier of the mutant gene will show a disease. Incomplete penetrance means that some carriers may not have symptoms.
- Expressiveness: The severity of the symptoms of the disease. Variable expressiveness means that symptoms can vary in gravity of different people with the same mutation.
II. Clinical methods for diagnosing hereditary diseases
The clinical assessment remains an important first step in the diagnosis of hereditary diseases.
- A history of anamnesis: A detailed history of the anamnesis, including family history, anamnesis of the mother’s pregnancy, the development of the child and current symptoms, can identify possible hereditary factors.
- Physical examination: A thorough physical examination can identify characteristic features and symptoms associated with specific hereditary diseases.
- Clinical signs and symptoms:
- Development of development: It may indicate chromosomal abnormalities or metabolic disorders.
- Dismorphism: The presence of unusual physical features, such as specific facial features, deformation of the limbs or anomalies of internal organs.
- Neurological symptoms: Convulsions, muscle weakness, loss of coordination, delay in mental development can be signs of hereditary neurological diseases.
- Metabolic disorders: Problems with digestion of food, fatigue, an unusual smell of body can indicate hereditary metabolic disorders.
- Heart disease: Congenital heart defects or cardiomyopathy can be hereditary.
- Family history: A thorough analysis of a family history for certain diseases or signs can help determine the inheritance model and evaluate the risk for other family members. The creation of a genealogical tree (pedigree) is an important tool.
- Risk assessment: Based on clinical data and family history, one can evaluate the risk of a hereditary disease and determine the need for further genetic testing.
III. Laboratory methods for the diagnosis of hereditary diseases
A wide range of laboratory tests is used to diagnose hereditary diseases, starting from biochemical analyzes and ending with complex genomic technologies.
- Biochemical tests:
- Newborns screening: The early identification of certain metabolic disorders (for example, phenylketonuria, galactosemia, congenital hypothyroidism) in newborns allows you to start treatment and prevent serious complications. Screening is usually carried out by taking a small blood sample from the heel of the newborn.
- Urine and blood analysis: The detection of abnormal levels of metabolites in the urine or blood may indicate hereditary metabolic disorders.
- Enzymes: Determining the activity of specific enzymes can help diagnose accumulation diseases (for example, Theya-Saxi disease, Gaucher disease).
- Cytogenetic methods:
- Cariotipirani: Analysis of chromosomes for identifying numerical (for example, trisomy 21 for Down syndrome) or structural (for example, translocation, deletion) anomalies. Chromosomes are stained and visualized under a microscope.
- Fluorescent in situ hybridization (Fish): It is used to detect specific chromosomal regions or genes using fluorescent probes. It allows you to identify microeditions and duplications that may not be visible during cariotrapy.
- Chromosomal micrust analysis (CMA): Detects deletions and duplications of DNA throughout the genome with higher resolution than carutping and Fish. It is widely used to diagnose the causes of developmental delay and congenital anomalies.
- Molecular methods:
- Polymerase chain reaction (PCR): Increases (amplified) certain areas of DNA, which allows further analysis. Widely used to detect mutations in genes.
- DNA sequencing: Determines the sequence of nucleotides in DNA.
- Senger sequencing: The traditional sequencing method used to analyze individual genes or small areas of DNA.
- New generation sequencing (NGS): Allows you to simultaneously secure many genes or even the entire genome. Revolutionized genetic diagnosis, making it possible to identify rare and complex genetic diseases. There are different types of NGS, including:
- Exom sequencing (WES): Only the encoding areas (exons) of genes, which make up about 1% of the genome, but contain most of the known mutations that cause diseases.
- Sequencing of the entire genome (WGS): Seenes the whole genome, including coding and non -dodging areas. It can identify mutations in non -dodging areas, which can also be the cause of diseases.
- Analysis of fragments: It is used to detect changes in the amount of certain DNA sections, for example, in the analysis of trinucleotide repetitions (for example, in the disease of Huntington, with a brittle x chromosome).
- MLPA (Multiplex Ligation-dependent Probe Amplification): The method used to detect changes in the number of copies of DNA (deletion or duplication) of specific genes or areas of the genome.
IV. Specialized methods for the diagnosis of hereditary diseases
Depending on the suspect disease, specialized diagnostic methods may be required.
- Diagnosis of metabolic diseases:
- Cultivation of fibroblasts: It is used to study the activity of enzymes and metabolic processes in skin cells.
- Organic acids of urine: Analysis to detect abnormal organic acids indicating specific metabolic defects.
- Plasma amino acids: Analysis to determine the level of amino acids in blood plasma, which may indicate disorders of amino acid metabolism.
- Carnitine analysis: Assessment of the level of cornitine necessary for transporting fatty acids to mitochondria for energy. Carnitine deficiency can lead to metabolic disorders.
- Diagnosis of neuromuscular diseases:
- Electromyography (EMG): It measures the electrical activity of muscles and nerves, helping to diagnose neuromuscular diseases.
- Muscle biopsy: The study of the sample of muscle tissue under a microscope to identify structural changes characteristic of certain neuromuscular diseases.
- Analysis of creatine (KC): An increased level of CC in the blood can indicate muscle damage characteristic of muscle dystrophy.
- Diagnosis of cyliopathies:
- Cellular epithelial cell cultivation: Studying the structure and functions of cilia that are important for many organs and systems, including the respiratory tract, kidneys and brain.
- Diagnosis of connective tissue disorders:
- Skin biopsy: The study of the skin sample under a microscope to assess the structure of collagen and other components of connective tissue.
- Echocardiography: Study of the heart with ultrasound to detect anomalies associated with impaired connective tissue, such as Marfan syndrome.
- Ophthalmological examination: Identification of eye anomalies, such as the dislocation of the lens, also characteristic of Martane syndrome.
- Diagnosis of immunodeficiency states:
- Immunophenotyping: Determination of types and the number of immune cells in the blood.
- Evaluation of the function of immune cells: Assessment of the ability of immune cells to function properly, for example, to produce antibodies or destroy pathogens.
V. Prenatal diagnosis of hereditary diseases
Prenatal diagnosis allows you to identify hereditary diseases in the fetus before birth.
- Non -invasive prenatal test (NIPT): Analysis of DNA of the fetus circulating in the blood of the mother to detect chromosomal abnormalities (for example, Down syndrome, Edwards syndrome, Patau syndrome) and some other genetic states. Non -invasive, as it only requires blood taking from the mother.
- Amniocentez: Taking a sample of amniotic fluid surrounding the fetus for genetic analysis. It is usually carried out between 15 and 20 weeks of pregnancy. Bends a small risk of miscarriage.
- Chorion Biopsy (BX): Taking a sample of chorion fabric (future placenta) for genetic analysis. It is usually carried out between 10 and 13 weeks of pregnancy. It carries a slightly greater risk of miscarriage than amniocentesis.
- Preimplantation genetic diagnostics (PGD): Genetic testing of embryos created in vitro (IVF) before implantation in the uterus. Allows you to choose embryos free from certain genetic diseases.
- Ultrasound study: Allows you to identify some structural anomalies of the fetus, which may indicate hereditary diseases. For example, the increased thickness of the collar space may indicate Down syndrome.
VI. Ethical aspects of genetic diagnostics
Genetic diagnosis raises a number of ethical issues that must be taken into account.
- Confidentiality: It is important to ensure the confidentiality of the patient’s genetic information.
- Informed consent: The patient should be fully informed about the goals, risks and advantages of genetic testing and give a conscious consent to the test.
- Discrimination: It is necessary to prevent discrimination based on genetic information in the field of employment, insurance and other areas.
- Psychological impact: The results of genetic testing can have a significant psychological effect on the patient and his family. It is important to ensure psychological support and counseling.
- EUGENIA: It is necessary to avoid the use of genetic information for the purposes of Eugenics aimed at “improving” the gene pool.
- Right to refuse: The patient has the right to abandon genetic testing.
- Accessibility: It is important to ensure the availability of genetic diagnostics for everyone who needs it, regardless of their socio-economic status.
VII. Genetic counseling
Genetic counseling is an important part of the process of diagnosing hereditary diseases.
- Risk assessment: The genetic consultant evaluates the risk of the presence or transfer of a hereditary disease based on a family history, clinical data and genetic testing results.
- Discussion of testing options: The genetic consultant explains various options for genetic testing, their advantages and disadvantages, and helps the patient choose the most suitable test.
- Interpretation of the results: The genetic consultant interprets the results of genetic testing and explains their significance for the patient and his family.
- Family planning: The genetic consultant provides information on family planning options, such as prenatal diagnostics, preimplantation genetic diagnostics and gametes.
- Psychological support: The genetic consultant provides psychological support to patients and their families, helping them cope with the emotional consequences of genetic testing and diagnosis of hereditary diseases.
- Recommendations: A genetic consultant can recommend that the patient contact other specialists such as geneticist, endocrinologists, neurologists, etc.
VIII. The future of genetic diagnostics
The area of genetic diagnostics is developing rapidly, offering new opportunities for the identification and treatment of hereditary diseases.
- Genomy: Reducing the cost and increasing the availability of genomic sequencing allows wider genomic testing for diagnosis and screening.
- Bioinformatics: The development of bioinformatics and machine learning algorithms allows you to more efficiently analyze huge volumes of genomic data and identify new genes and mutations associated with diseases.
- Genomic editing (CRISPR-CAS9): CRISPR-CAS9 genomic editing technology offers the potential for the treatment of hereditary diseases by correcting mutant genes. However, the technology is still in the early stages of development and requires further research.
- Personalized medicine: Genetic information can be used to develop individual treatment plans based on the patient’s genetic profile.
- Development of new drugs: The identification of genes and mutations that cause diseases allows you to develop new drugs aimed at specific genetic defects.
- Early diagnosis and prevention: Early diagnosis of hereditary diseases allows you to start treatment in a timely manner and prevent serious complications. Genetic screening can help identify people at risk of developing certain diseases, and take preventive measures.
IX. Final considerations
Diagnosis of hereditary diseases is a complex and multifaceted process that requires the integration of clinical information, laboratory data and genetic counseling. The constant development of genetic technologies opens up new opportunities for the identification and treatment of hereditary diseases, improving the health and quality of life of patients and their families. It is necessary to take into account the ethical aspects of genetic diagnostics and ensure the availability and confidentiality of genetic information. Continuing research and development in the field of genetics promise significant improvements in the diagnosis, treatment and prevention of hereditary diseases in the future.