Successful bilateral lung transplantation in pulmonary alveolar microlithiasis: A case report and review of literature.

BACKGROUND: Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive genetic disorder with approximately 1000 known cases worldwide, in which calcium phosphate microliths deposit in the alveolar air spaces. As of writing this report, no definitive conventional therapy exists, and many PAM cases may progress to severe respiratory failure and potential death. Bilateral lung transplantation (BLx) seems to be the most optimal solution; however, this procedure is challenging along with limited reports regarding the outcome in PAM. We report a case of PAM successfully treated with BLx for the first time in Iran. METHOD: We present the case of a 42-year-old female with a longstanding history of cough, not responding to conventional antitussive medication, who was diagnosed as a case of PAM following a hospitalization due to coughing, dyspnea on exertion, and hemoptysis. Despite treatment with corticosteroid and medical treatment, no improvement was achieved and she subsequently developed respiratory and right ventricular failure, with oxygen ventilation dependence. Eventually, she was scheduled for BLx. The operation was successful and during her 2-year follow-up, no recurrence or significant postoperative complications has been reported. CONCLUSION: This case presentation and literature review confirm the effectiveness of BLx as a promising treatment for PAM-diagnosed patients, improving both life expectancy and quality of life.

An algorithm to identify patients aged 0-3 with rare genetic disorders.

BACKGROUND: With over 7000 Mendelian disorders, identifying children with a specific rare genetic disorder diagnosis through structured electronic medical record data is challenging given incompleteness of records, inaccurate medical diagnosis coding, as well as heterogeneity in clinical symptoms and procedures for specific disorders. We sought to develop a digital phenotyping algorithm (PheIndex) using electronic medical records to identify children aged 0-3 diagnosed with genetic disorders or who present with illness with an increased risk for genetic disorders. RESULTS: Through expert opinion, we established 13 criteria for the algorithm and derived a score and a classification. The performance of each criterion and the classification were validated by chart review. PheIndex identified 1,088 children out of 93,154 live births who may be at an increased risk for genetic disorders. Chart review demonstrated that the algorithm achieved 90% sensitivity, 97% specificity, and 94% accuracy. CONCLUSIONS: The PheIndex algorithm can help identify when a rare genetic disorder may be present, alerting providers to consider ordering a diagnostic genetic test and/or referring a patient to a medical geneticist.

[Analysis of the results for genetic disease screening among 1 000 newborns from Huzhou].

OBJECTIVE: To analyze the types and distribution of pathogenic variants for neonatal genetic diseases in Huzhou, Zhejiang Province. METHODS: One thousand neonates (48 ~ 42 h after birth) born to Huzhou region were selected as the study subjects. Dry blood spot samples were collected from the newborns, and targeted capture high-throughput sequencing was carried out for pathogenic genes underlying 542 inherited diseases. Candidate variants were verified by Sanger sequencing. RESULTS: Among the 1 000 newborns, the male to female ratio was 1.02 : 1.00. No pathogenic variants were detected in 253 cases, whilst 747 cases were found to carry at least one pathogenic variant, which yielded a carrier rate of 74.7%. The most frequently involved pathogenic gene was FLG, followed by GJB2, UGT1A1, USH2A and DUOX2. The variants were classified as homozygous, compound heterozygous, and hemizygous variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), 213 neonates were verified to have carried pathogenic and/or likely pathogenic variants, with a positive rate of 21.3%. The most commonly involved genes had included UGT1A1, FLG, GJB2, MEFV and G6PD. CONCLUSION: Newborn screening based on high-throughput sequencing technology can expand the scope of screening and improve the positive predictive value. Genetic counseling based on the results can improve the patients' medical care and reduce neonatal mortality and childhood morbidity, while provide assistance to family members' health management and reproductive decisions.

A propósito de un caso de síndrome de Fraser. Autopsia de un feto de 37 semanas de gestación con múltiples malformaciones / About a case of Fraser syndrome. Autopsy of a 37 weeks gestation fetus with multiple malformations

El síndrome de Fraser o síndrome criptoftalmos/sindactilia es una enfermedad genética rara, cuyo diagnóstico se basa en una serie de criterios clínicos mayores y menores, y que puede apoyarse en pruebas genéticas. En este artículo se presenta el caso de una autopsia fetal de 37 semanas de gestación con sospecha de síndrome de CHAOS (síndrome obstructivo congénito de las vías aéreas altas). (AU)

Fraser syndrome or cryptophthalmos-syndactyly syndrome is a rare genetic disease, the diagnosis of which is based on a series of major and minor clinical criteria and that can be supported by genetic tests. This article presents the case of a fetal autopsy at 37 weeks of gestation with suspicion of CHAOS syndrome (congenital obstructive syndrome of the upper airways). (AU)

A propósito de un caso de síndrome de Fraser. Autopsia de un feto de 37 semanas de gestación con múltiples malformaciones / About a case of Fraser syndrome. Autopsy of a 37 weeks gestation fetus with multiple malformations

El síndrome de Fraser o síndrome criptoftalmos/sindactilia es una enfermedad genética rara, cuyo diagnóstico se basa en una serie de criterios clínicos mayores y menores, y que puede apoyarse en pruebas genéticas. En este artículo se presenta el caso de una autopsia fetal de 37 semanas de gestación con sospecha de síndrome de CHAOS (síndrome obstructivo congénito de las vías aéreas altas). (AU)

Fraser syndrome or cryptophthalmos-syndactyly syndrome is a rare genetic disease, the diagnosis of which is based on a series of major and minor clinical criteria and that can be supported by genetic tests. This article presents the case of a fetal autopsy at 37 weeks of gestation with suspicion of CHAOS syndrome (congenital obstructive syndrome of the upper airways). (AU)

Clinical Guideline for Preimplantation Genetic Testing in Inherited Cardiac Diseases.

BACKGROUND: Preimplantation genetic testing (PGT) is a reproductive technology that selects embryos without (familial) genetic variants. PGT has been applied in inherited cardiac disease and is included in the latest American Heart Association/American College of Cardiology guidelines. However, guidelines selecting eligible couples who will have the strongest risk reduction most from PGT are lacking. We developed an objective decision model to select eligibility for PGT and compared its results with those from a multidisciplinary team. METHODS: All couples with an inherited cardiac disease referred to the national PGT center were included. A multidisciplinary team approved or rejected the indication based on clinical and genetic information. We developed a decision model based on published risk prediction models and literature, to evaluate the severity of the cardiac phenotype and the penetrance of the familial variant in referred patients. The outcomes of the model and the multidisciplinary team were compared in a blinded fashion. RESULTS: Eighty-three couples were referred for PGT (1997-2022), comprising 19 different genes for 8 different inherited cardiac diseases (cardiomyopathies and arrhythmias). Using our model and proposed cutoff values, a definitive decision was reached for 76 (92%) couples, aligning with 95% of the multidisciplinary team decisions. In a prospective cohort of 11 couples, we showed the clinical applicability of the model to select couples most eligible for PGT. CONCLUSIONS: The number of PGT requests for inherited cardiac diseases increases rapidly, without the availability of specific guidelines. We propose a 2-step decision model that helps select couples with the highest risk reduction for cardiac disease in their offspring after PGT.

El manejo multidisciplinar mejora el diagnóstico genético de las enfermedades renales hereditarias en la era de next generation sequencing (NGS) / Multidisciplinary management improves the genetic diagnosis of hereditary kidney diseases in the next generation sequencing (NGS) era

Antecedentes y objetivo Las enfermedades renales hereditarias (ERH) son una causa frecuente de enfermedad renal crónica, habiéndose incrementado su diagnóstico desde la introducción de la secuenciación masiva (NGS). En 2018 se fundó la Unidad multidisciplinar de Enfermedades Renales Hereditarias de la Región de Murcia basándose en el estudio genético de las ERH mediante panel de genes. El objetivo de este estudio es analizar los resultados obtenidos en los primeros tres años de funcionamiento, así como analizar los factores clínicos que se asocian a la obtención de un diagnóstico genético final. Materiales y métodos Se incluyeron los pacientes estudiados mediante panel de genes de ERH y se compararon las características entre los que obtuvieron un diagnóstico genético final y los que no. Resultados Se estudiaron un total de 360 pacientes, detectándose variantes genéticas en 164 pacientes (45,6%) no relacionados familiarmente. Cuarenta y cinco de estas variantes eran de significado clínico incierto precisando estudio de cosegregación familiar, facilitado por la unidad multidisciplinar. Globalmente, considerando los resultados obtenidos con el panel de NGS realizado en el CBGC y los estudios genómicos ampliados, se consiguió un rendimiento diagnóstico final de ERH del 33,3% (120/360), contando hallazgos incidentales, del 35,6% (128/360). Se estudiaron 223 pacientes con sospecha de síndrome de Alport, confirmándose el diagnóstico en un 28,5% (gen más frecuente COL4A4), los cuales eran con más frecuencia mujeres, y con clara historia familiar compatible. También tenían con más frecuencia microhematuria, aunque 5 pacientes sin microhematuria confirmaron diagnóstico. No hubo diferencias en la edad, proteinuria, función renal, hipoacusia o alteraciones oftalmológicas (AU)

Background and objective Hereditary kidney diseases (HKD) are a frequent cause of chronic kidney disease, and their diagnosis has increased since the introduction of next generation sequencing (NGS). In 2018, the Multidisciplinary Unit for Hereditary Kidney Diseases of the Region of Murcia (UMERH-RM) was founded based on the genetic study of HKD. The objective of this study is to analyze the results obtained in the first 3 years of operation, and to analyze the clinical factors associated to a final genetic diagnosis. Materials and methods All the patients studied with the HKD gene panel were included. The characteristics between those who obtained a final genetic diagnosis and those who did not were compared. Results A total of 360 patients were studied, detecting genetic variants in 164 not related patients (45.6%). 45 of these were variants of uncertain significance requiring a family co-segregation study, which was facilitated by the multidisciplinary unit. Overall, considering the results obtained with the NGS panel and the extended genomic studies, a final diagnostic yield of HRD of 33.3% (120/360) was achieved, and including incidental findings 35.6% (128/360). Two hundred and twenty-three patients with suspected Alport syndrome were studied. Diagnosis was confirmed in 28.5% (COL4A4 most frequent gene), more frequently women with an obvious compatible family history. They also had frequently microhematuria, although 5 patients without microhematuria confirmed the diagnosis. There were no differences in age, proteinuria, renal function, hearing loss, or ophthalmologic abnormalities. The most frequent finding in the renal biopsy was mesangial proliferation. We estimate that 39 patients avoided renal biopsy (AU)

'If I Knew More I Would Feel Less Worried': Filipino Americans' Attitudes and Knowledge of Genetic Disease, Counseling, and Testing.

INTRODUCTION: The field of genetics is rapidly expanding and people are increasingly utilizing genetic testing and counseling services. However, the current literature on genetic health topics and Filipinos remains limited, as many minority populations are not adequately studied. This study describes Filipino Americans' attitudes and knowledge of genetic disease, genetic testing, and genetic counseling. To address these knowledge gaps and reduce the burden of health disparities, the informational needs of Filipino Americans regarding genetic disease and genetic services must be understood in order to better tailor these services and outreach methods. METHODS: Fifteen semi-structured, qualitative interviews were held with individuals who self-identified as Filipino American between November 2022 and January 2023. Interviews were transcribed and coded using an iterative process. RESULTS: Most participants were familiar with genetic disease and believed that factors such as biology, as well as cultural factors such as upbringing and food, contributed to its development. The majority of participants had previously heard of genetic testing; however, most participants either did not know much or were only familiar with ancestry direct-to-consumer genetic testing (DTC-GT). Most participants had not heard of genetic counseling and those that had heard of genetic counseling before did not understand its purpose. Overall, most participants had a positive attitude toward genetic testing and counseling. Participants identified the benefits of these services including genetic disease prevention, management, and treatment. Participants stressed the importance of educating the Filipino community and shared their ideas for how to implement outreach efforts. DISCUSSION/CONCLUSION: This study found that Filipino Americans generally had a positive outlook on genetic testing and genetic counseling. We propose participant-generated ideas for outreach and education that may help inform future public health efforts that aim to educate this population about genetic disease, testing and counseling.

Whole genome sequencing as a first-tier diagnostic test for infants in neonatal intensive care units: A pilot study in Brazil.

In this pilot study, we aimed to evaluate the feasibility of whole genome sequencing (WGS) as a first-tier diagnostic test for infants hospitalized in neonatal intensive care units in the Brazilian healthcare system. The cohort presented here results from a joint collaboration between private and public hospitals in Brazil considering the initiative of a clinical laboratory to provide timely diagnosis for critically ill infants. We performed trio (proband and parents) WGS in 21 infants suspected of a genetic disease with an urgent need for diagnosis to guide medical care. Overall, the primary indication for genetic testing was dysmorphic syndromes (n = 14, 67%) followed by inborn errors of metabolism (n = 6, 29%) and skeletal dysplasias (n = 1, 5%). The diagnostic yield in our cohort was 57% (12/21) based on cases that received a definitive or likely definitive diagnostic result from WGS analysis. A total of 16 pathogenic/likely pathogenic variants and 10 variants of unknown significance were detected, and in most cases inherited from an unaffected parent. In addition, the reported variants were of different types, but mainly missense (58%) and associated with autosomal diseases (19/26); only three were associated with X-linked diseases, detected in hemizygosity in the proband an inherited from an unaffected mother. Notably, we identified 10 novel variants, absent from public genomic databases, in our cohort. Considering the entire diagnostic process, the average turnaround time from enrollment to medical report in our study was 53 days. Our findings demonstrate the remarkable utility of WGS as a diagnostic tool, elevating the potential of transformative impact since it outperforms conventional genetic tests. Here, we address the main challenges associated with implementing WGS in the medical care system in Brazil, as well as discuss the potential benefits and limitations of WGS as a diagnostic tool in the neonatal care setting.

Liver Transplantation in a Woman with Mahvash Disease.

Mahvash disease is an exceedingly rare genetic disorder of glucagon signaling characterized by hyperglucagonemia, hyperaminoacidemia, and pancreatic α-cell hyperplasia. Although there is no known definitive treatment, octreotide has been used to decrease systemic glucagon levels. We describe a woman who presented to our medical center after three episodes of small-volume hematemesis. She was found to have hyperglucagonemia and pancreatic hypertrophy with genetically confirmed Mahvash disease and also had evidence of portal hypertension (recurrent portosystemic encephalopathy and variceal hemorrhage) in the absence of cirrhosis. These findings established a diagnosis of portosinusoidal vascular disease, a presinusoidal type of portal hypertension previously known as noncirrhotic portal hypertension. Liver transplantation was followed by normalization of serum glucagon and ammonia levels, reversal of pancreatic hypertrophy, and resolution of recurrent encephalopathy and bleeding varices.

Bombardier Blood (2020): Un documental más allá de la enfermedad / Bombardier Blood (2020): A Documentary beyond the Illness

Si bien la hemofilia era conocida como una enfermedad que perturbaba solo a las familias reales de Europa, actualmente afecta a uno de cada 5.000 y a uno de cada 30.000 varones recién nacidos vivos tanto para la de Tipo A como B, respectivamente. La hemofilia es un trastorno de la coagulación sanguínea que afecta principalmente a varones por su carácter de herencia recesiva ligada al X, siendo su manifestación principal las hemorragias que pueden llegar a ser mortales si no son tratadas correctamente. En Bombardier Blood (2020) de Patrick James Lynch, un documental enfocado al recorrido de Chris Bombardier, una persona hemofílica cuyo sueño es escalar las siete cumbres más altas del mundo, incluyendo en su paso el monte Everest en el Himalaya. El documental además de destacar los aspectos médicos sobre esta enfermedad hace ver los diferentes estilos de vida de acuerdo a su localización, las normativas y sistemas de salud que los rige y como esto incide en el diagnóstico, seguimiento y tratamiento. (AU)

While hemophilia was considered a disease that disturbed only the royal families of Europe, it currently affects one in 5.000 and one in 30.000 live newborn males for both Type A and B, respectively. Hemophilia is a blood clotting disorder that mainly affects men due to its character of recessive inheritance linked to X, its main manifestation hemorrhaging that can become fatal if they are not treated correctly. Bombardier Blood (2020) by Patrick James Lynch is a documentary focused on the journey of Chris Bombardier, a hemophilic person whose dream is to climb the seven highest summits in the world, including Mount Everest in the Himalayas. The documentary, in addition to highlighting the medical aspects of this disease, shows the different lifestyles according to their location, the regulations and health systems that govern them, and how these affect diagnosis, monitoring, and treatment. (AU)

Rates and Classification of Variants of Uncertain Significance in Hereditary Disease Genetic Testing.

Importance: Variants of uncertain significance (VUSs) are rampant in clinical genetic testing, frustrating clinicians, patients, and laboratories because the uncertainty hinders diagnoses and clinical management. A comprehensive assessment of VUSs across many disease genes is needed to guide efforts to reduce uncertainty. Objective: To describe the sources, gene distribution, and population-level attributes of VUSs and to evaluate the impact of the different types of evidence used to reclassify them. Design, Setting, and Participants: This cohort study used germline DNA variant data from individuals referred by clinicians for diagnostic genetic testing for hereditary disorders. Participants included individuals for whom gene panel testing was conducted between September 9, 2014, and September 7, 2022. Data were analyzed from September 1, 2022, to April 1, 2023. Main Outcomes and Measures: The outcomes of interest were VUS rates (stratified by age; clinician-reported race, ethnicity, and ancestry groups; types of gene panels; and variant attributes), percentage of VUSs reclassified as benign or likely benign vs pathogenic or likely pathogenic, and enrichment of evidence types used for reclassifying VUSs. Results: The study cohort included 1 689 845 individuals ranging in age from 0 to 89 years at time of testing (median age, 50 years), with 1 203 210 (71.2%) female individuals. There were 39 150 Ashkenazi Jewish individuals (2.3%), 64 730 Asian individuals (3.8%), 126 739 Black individuals (7.5%), 5539 French Canadian individuals (0.3%), 169 714 Hispanic individuals (10.0%), 5058 Native American individuals (0.3%), 2696 Pacific Islander individuals (0.2%), 4842 Sephardic Jewish individuals (0.3%), and 974 383 White individuals (57.7%). Among all individuals tested, 692 227 (41.0%) had at least 1 VUS and 535 385 (31.7%) had only VUS results. The number of VUSs per individual increased as more genes were tested, and most VUSs were missense changes (86.6%). More VUSs were observed per sequenced gene in individuals who were not from a European White population, in middle-aged and older adults, and in individuals who underwent testing for disorders with incomplete penetrance. Of 37 699 unique VUSs that were reclassified, 30 239 (80.2%) were ultimately categorized as benign or likely benign. A mean (SD) of 30.7 (20.0) months elapsed for VUSs to be reclassified to benign or likely benign, and a mean (SD) of 22.4 (18.9) months elapsed for VUSs to be reclassified to pathogenic or likely pathogenic. Clinical evidence contributed most to reclassification. Conclusions and Relevance: This cohort study of approximately 1.6 million individuals highlighted the need for better methods for interpreting missense variants, increased availability of clinical and experimental evidence for variant classification, and more diverse representation of race, ethnicity, and ancestry groups in genomic databases. Data from this study could provide a sound basis for understanding the sources and resolution of VUSs and navigating appropriate next steps in patient care.

Rapid Whole-Genomic Sequencing and a Targeted Neonatal Gene Panel in Infants With a Suspected Genetic Disorder.

Importance: Genomic testing in infancy guides medical decisions and can improve health outcomes. However, it is unclear whether genomic sequencing or a targeted neonatal gene-sequencing test provides comparable molecular diagnostic yields and times to return of results. Objective: To compare outcomes of genomic sequencing with those of a targeted neonatal gene-sequencing test. Design, Setting, and Participants: The Genomic Medicine for Ill Neonates and Infants (GEMINI) study was a prospective, comparative, multicenter study of 400 hospitalized infants younger than 1 year of age (proband) and their parents, when available, suspected of having a genetic disorder. The study was conducted at 6 US hospitals from June 2019 to November 2021. Exposure: Enrolled participants underwent simultaneous testing with genomic sequencing and a targeted neonatal gene-sequencing test. Each laboratory performed an independent interpretation of variants guided by knowledge of the patient's phenotype and returned results to the clinical care team. Change in clinical management, therapies offered, and redirection of care was provided to families based on genetic findings from either platform. Main Outcomes and Measures: Primary end points were molecular diagnostic yield (participants with ≥1 pathogenic variant or variant of unknown significance), time to return of results, and clinical utility (changes in patient care). Results: A molecular diagnostic variant was identified in 51% of participants (n = 204; 297 variants identified with 134 being novel). Molecular diagnostic yield of genomic sequencing was 49% (95% CI, 44%-54%) vs 27% (95% CI, 23%-32%) with the targeted gene-sequencing test. Genomic sequencing did not report 19 variants found by the targeted neonatal gene-sequencing test; the targeted gene-sequencing test did not report 164 variants identified by genomic sequencing as diagnostic. Variants unidentified by the targeted genomic-sequencing test included structural variants longer than 1 kilobase (25.1%) and genes excluded from the test (24.6%) (McNemar odds ratio, 8.6 [95% CI, 5.4-14.7]). Variant interpretation by laboratories differed by 43%. Median time to return of results was 6.1 days for genomic sequencing and 4.2 days for the targeted genomic-sequencing test; for urgent cases (n = 107) the time was 3.3 days for genomic sequencing and 4.0 days for the targeted gene-sequencing test. Changes in clinical care affected 19% of participants, and 76% of clinicians viewed genomic testing as useful or very useful in clinical decision-making, irrespective of a diagnosis. Conclusions and Relevance: The molecular diagnostic yield for genomic sequencing was higher than a targeted neonatal gene-sequencing test, but the time to return of routine results was slower. Interlaboratory variant interpretation contributes to differences in molecular diagnostic yield and may have important consequences for clinical management.

Carrier burden of over 300 diseases in Han Chinese identified by expanded carrier testing of 300 couples using assisted reproductive technology.

BACKGROUND: Expanded carrier screening (ECS) has become a common practice for identifying carriers of monogenic diseases. However, existing large gene panels are not well-tailored to Chinese populations. In this study, ECS testing for pathogenic variants of both single-nucleotide variants (SNVs) and copy number variants (CNVs) in 330 genes implicated in 342 autosomal recessive (AR) or X-linked diseases was carried out. We assessed the differences in allele frequencies specific to the Chinese population who have used assisted reproductive technology (ART) and the important genes to screen for in this population. METHODOLOGY: A total of 300 heterosexual couples were screened by our ECS panel using next-generation sequencing. A customed bioinformatic algorithm was used to analyze SNVs and CNVs. Guidelines from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology were adapted for variant interpretation. Pathogenic or likely pathogenic (P/LP) SNVs located in high homology regions/deletions and duplications of one or more exons in length were independently verified with other methods. RESULTS: 64.83% of the patients were identified to be carriers of at least one of 342 hereditary conditions. We identified 622 P/LP variants, 4.18% of which were flagged as CNVs. The rate of at-risk couples was 3%. A total of 149 AR diseases accounted for 64.05% of the cumulative carrier rate, and 48 diseases had a carrier rate above 1/200 in the test. CONCLUSION: An expanded screening of inherited diseases by incorporating different variant types, especially CNVs, has the potential to reduce the occurrence of severe monogenic diseases in the offspring of patients using ART in China.

Implementación asistencial de estudios genómicos aplicados al diagnóstico molecular / Implementation of genomic studies applied to molecular diagnostics

El Hospital Garrahan ha sido pionero en el diagnóstico molecular de patologías pediátricas en Argentina. Los avances tecnológicos de las últimas décadas en el área de la biología molecular, sentaron las bases para la optimización y ampliación del diagnóstico molecular a partir de la secuenciación masiva en paralelo de múltiples genes. El presente trabajo describe el proceso de implementación de los estudios de secuenciación de nueva generación y el desarrollo de la Unidad de Genómica en un hospital público pediátrico de alta complejidad, así como su impacto en las capacidades diagnósticas de enfermedades poco frecuentes de origen genético. La creación del Grupo Interdisciplinario de Estudios Genómicos constituyó la vía institucional para la toma de decisiones que implican la implementación de nuevos estudios genómicos y el establecimiento de prioridades diagnósticas, extendiendo la disponibilidad del diagnóstico molecular a más disciplinas. La Unidad de Genómica trabaja en diseñar las estrategias que permitan la mayor optimización de los recursos con los que cuenta el hospital, teniendo en cuenta el equipamiento disponible, las prioridades establecidas y la frecuencia de las distintas patologías. Se demuestra el salto significativo operado en nuestras capacidades diagnósticas, tanto en la variedad de enfermedades como en el número de genes analizados, habiendo estudiado a la fecha alrededor de 2.000 pacientes, muchos de los cuales ven de este modo finalizada su odisea diagnóstica. Los estudios de NGS se han convertido en una herramienta de la práctica diaria para la atención de un número importante de pacientes de nuestro hospital. Continuaremos trabajando para ampliar su aplicación a la mayor cantidad de patologías, a través de los mecanismos institucionales ya existentes (AU)

The Garrahan Hospital has been a pioneer in the molecular diagnosis of pediatric diseases in Argentina. The technological advances of the last decades in the area of molecular biology have laid the foundations for the optimization and expansion of molecular diagnostics through massive parallel sequencing of multiple genes. This study describes the process of implementation of next-generation sequencing studies and the development of the Genomics Unit in a public pediatric tertiary hospital, and its impact on the capacity to diagnose rare diseases of genetic origin. The creation of the Interdisciplinary Group of Genomic Studies constituted the institutional pathway for decision-making involving the implementation of new genomic studies and the establishment of diagnostic priorities, extending the availability of molecular diagnostics to additional disciplines. The Genomics Unit is working to design strategies that allow for optimization of the resources available to the hospital, taking into account the equipment available, the priorities established, and the frequency of the different diseases. It demonstrates the significant leap in our diagnostic capabilities, both in the variety of diseases and in the number of genes analyzed. To date, around 2,000 patients have been studies, many of whom have thus completed their diagnostic odyssey. NGS studies have become a tool in daily practice for the care of a significant number of patients in our hospital. We will continue working to expand its application to as many diseases as possible, through the existing institutional mechanisms (AU)