Use of Exome Sequencing as a First-Line Test in a Reference Center for Rare Diseases in Northeastern Brazil.
Health Services and Implementation
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Primary Categories:
- Genomic Medicine
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Secondary Categories:
- Genomic Medicine
Introduction:
In recent decades, advances in medical genetics have revolutionized the ability to identify genetic variants associated with a wide range of clinical conditions, especially in individuals with rare diseases. Exome sequencing, which analyzes DNA coding regions responsible for most known pathogenic variants, has become an essential diagnostic tool for identifying genetic anomalies in this context. This technique allows for a more targeted focus on regions that directly affect protein production, improving efficiency and accuracy in detecting genetic variants that impact health.
The introduction of next-generation sequencing (NGS) technologies has further enhanced the identification of genetic variants. By providing fast and high-throughput sequencing capabilities, NGS has enabled an in-depth study of complex disorders and increased the potential for accurate diagnoses, essential in rare and genetic diseases. Studies show that exome sequencing has been particularly effective for monogenic and Mendelian inheritance diseases, while also offering valuable insights into the pathogenesis of these conditions.
The combination of exome sequencing with CNV analysis has proven particularly advantageous, as it provides a more comprehensive view of underlying genetic causes, increasing diagnostic yield for rare and complex conditions. Kearney et al. (2011) indicated that the inclusion of CNVs enhances genetic identification capabilities, supporting personalized treatments and, in many cases, offering a clearer prognosis for patients.
In Brazil, particularly in the Northeast, the need for precise diagnoses for rare diseases has grown, driven by the demand for personalized and appropriate clinical interventions. Applying exome sequencing combined with CNV analysis in reference centers offers an alternative to improve patient care and outcomes, especially in regions facing access challenges and limited resources.
Methods:
This study is characterized as a retrospective observational study conducted in a pediatric reference hospital for rare diseases located in Northeastern Brazil. Data collection took place between October 2023 and May 2024, covering patients seen in the hospital's medical genetics outpatient clinic. The study population consisted of 40 patients, 20 female and 20 male, referred for molecular investigation due to suspected genetic diseases. Clinical indications for patient referral were classified into the following categories: Nephrology, Hematology/Immunology, Endocrinology, Inborn Errors of Metabolism, Gastroenterology/Hepatology, Neurodevelopmental Disorders, Pulmonology, and Dysmorphology.
Results:
Implementing exome sequencing as a first-line diagnostic tool in a reference center for rare diseases is a promising approach, especially in regions like Northeastern Brazil, where genetic diversity and limited access to specialized diagnostics affect the early and accurate identification of genetic diseases. Exome sequencing, by enabling detailed analysis of gene-coding regions, demonstrated effectiveness in our study with a diagnostic yield of 66.6% (26/40). Positive results were observed in 28 patients, of whom 7.1% (2/28) had variants associated with CNVs (Copy Number Variants). This finding highlights the importance of including complementary CNV analyses alongside exome sequencing to capture structural variants relevant to genetic diseases.
Conclusion:
The use of exome sequencing as an initial diagnostic tool has proven advantageous in optimizing resources, reducing diagnostic time, and enabling more effective patient management. This practice reduces the need for prolonged and costly clinical investigations, promoting early and specific interventions essential for managing rare diseases. The inclusion of exome sequencing also expands knowledge of the genetic diversity of the Brazilian population, which is characterized by heterogeneity and underrepresentation in global genetic studies.
Thus, the experience described here emphasizes the usefulness of exome sequencing as a first-line tool, particularly beneficial in areas with limited access to advanced technologies, reducing regional disparities in the diagnosis and treatment of rare diseases in Brazil.
In recent decades, advances in medical genetics have revolutionized the ability to identify genetic variants associated with a wide range of clinical conditions, especially in individuals with rare diseases. Exome sequencing, which analyzes DNA coding regions responsible for most known pathogenic variants, has become an essential diagnostic tool for identifying genetic anomalies in this context. This technique allows for a more targeted focus on regions that directly affect protein production, improving efficiency and accuracy in detecting genetic variants that impact health.
The introduction of next-generation sequencing (NGS) technologies has further enhanced the identification of genetic variants. By providing fast and high-throughput sequencing capabilities, NGS has enabled an in-depth study of complex disorders and increased the potential for accurate diagnoses, essential in rare and genetic diseases. Studies show that exome sequencing has been particularly effective for monogenic and Mendelian inheritance diseases, while also offering valuable insights into the pathogenesis of these conditions.
The combination of exome sequencing with CNV analysis has proven particularly advantageous, as it provides a more comprehensive view of underlying genetic causes, increasing diagnostic yield for rare and complex conditions. Kearney et al. (2011) indicated that the inclusion of CNVs enhances genetic identification capabilities, supporting personalized treatments and, in many cases, offering a clearer prognosis for patients.
In Brazil, particularly in the Northeast, the need for precise diagnoses for rare diseases has grown, driven by the demand for personalized and appropriate clinical interventions. Applying exome sequencing combined with CNV analysis in reference centers offers an alternative to improve patient care and outcomes, especially in regions facing access challenges and limited resources.
Methods:
This study is characterized as a retrospective observational study conducted in a pediatric reference hospital for rare diseases located in Northeastern Brazil. Data collection took place between October 2023 and May 2024, covering patients seen in the hospital's medical genetics outpatient clinic. The study population consisted of 40 patients, 20 female and 20 male, referred for molecular investigation due to suspected genetic diseases. Clinical indications for patient referral were classified into the following categories: Nephrology, Hematology/Immunology, Endocrinology, Inborn Errors of Metabolism, Gastroenterology/Hepatology, Neurodevelopmental Disorders, Pulmonology, and Dysmorphology.
Results:
Implementing exome sequencing as a first-line diagnostic tool in a reference center for rare diseases is a promising approach, especially in regions like Northeastern Brazil, where genetic diversity and limited access to specialized diagnostics affect the early and accurate identification of genetic diseases. Exome sequencing, by enabling detailed analysis of gene-coding regions, demonstrated effectiveness in our study with a diagnostic yield of 66.6% (26/40). Positive results were observed in 28 patients, of whom 7.1% (2/28) had variants associated with CNVs (Copy Number Variants). This finding highlights the importance of including complementary CNV analyses alongside exome sequencing to capture structural variants relevant to genetic diseases.
Conclusion:
The use of exome sequencing as an initial diagnostic tool has proven advantageous in optimizing resources, reducing diagnostic time, and enabling more effective patient management. This practice reduces the need for prolonged and costly clinical investigations, promoting early and specific interventions essential for managing rare diseases. The inclusion of exome sequencing also expands knowledge of the genetic diversity of the Brazilian population, which is characterized by heterogeneity and underrepresentation in global genetic studies.
Thus, the experience described here emphasizes the usefulness of exome sequencing as a first-line tool, particularly beneficial in areas with limited access to advanced technologies, reducing regional disparities in the diagnosis and treatment of rare diseases in Brazil.