Revistas
Revista:
PEDIATRIC DERMATOLOGY
ISSN:
0736-8046
Año:
2023
Vol.:
40
N°:
3
Págs.:
534 - 536
Pathogenic sequence changes in mitochondrial DNA (mtDNA) are one of the most common causes of genetic hearing loss. We report an infant with palmoplantar hyperkeratosis, extrapalmoplantar cutaneous features and mitochondrial sensorineural hearing loss caused by the previously reported pathogenic NC_012920:m.7445A > G sequence change in the mitochondrial gene COX1 (COX1, MT-CO1). Next generation sequencing- based technology was key for the diagnosis and management of this patient.
Revista:
FRONTIERS IN GENETICS
ISSN:
1664-8021
Año:
2023
Vol.:
14
Págs.:
1264899
Background: An early etiological diagnosis of hearing loss positively impacts children's quality of life including language and cognitive development. Even though hearing loss associates with extremely high genetic and allelic heterogeneity, several studies have proven that Next-Generation Sequencing (NGS)-based gene panel testing significantly reduces the time between onset and diagnosis. Methods: In order to assess the clinical utility of our custom NGS GHELP panel, the prevalence of pathogenic single nucleotide variants, indels or copy number variants was assessed by sequencing 171 nuclear and 8 mitochondrial genes in 155 Spanish individuals with hearing loss. Results: A genetic diagnosis of hearing loss was achieved in 34% (52/155) of the individuals (5 out of 52 were syndromic). Among the diagnosed cases, 87% (45/52) and 12% (6/52) associated with autosomal recessive and dominant inheritance patterns respectively; remarkably, 2% (1/52) associated with mitochondrial inheritance pattern. Although the most frequently mutated genes in this cohort were consistent with those described in the literature (GJB2, OTOF or MYO7A), causative variants in less frequent genes such as TMC1, FGF3 or mitCOX1 were also identified. Moreover, 5% of the diagnosed cases (3/52) were associated with pathogenic copy number variants. Conclusion: The clinical utility of NGS panels that allows identification of different types of pathogenic variants-not only single nucleotide variants/indels in both nuclear and mitochondrial genes but also copy number variants-has been demonstrated to reduce the clinical diagnostic odyssey in hearing loss. Thus, clinical implementation of genomic strategies within the regular clinical practice, and, more significantly, within the newborn screening protocols, is warranted.
Revista:
CANCERS
ISSN:
2072-6694
Año:
2021
Vol.:
13
N°:
21
Págs.:
5436
Simple Summary: Clinical management of sarcomas is complex because they are rare and heterogeneous tumors. Management requires a coordinated multidisciplinary approach, especially in children. Genomic characterization of this complex group of tumors contributes to the identification of prognostic biomarkers and to the continued expansion of therapeutic options. In this article, we present the positive experience of two Spanish hospitals in the use of genomic analysis in the overall clinical management of sarcomas in children and young adults. We describe on a case-by-case basis how genomic analysis has contributed to both diagnosis and treatment.Genomic techniques enable diagnosis and management of children and young adults with sarcomas by identifying high-risk patients and those who may benefit from targeted therapy or participation in clinical trials. Objective: to analyze the performance of an NGS gene panel for the clinical management of pediatric sarcoma patients. We studied 53 pediatric and young adult patients diagnosed with sarcoma, from two Spanish centers. Genomic data were obtained using the Oncomine Childhood Cancer Research Assay, and categorized according to their diagnostic, predictive, or prognostic value. In 44 (83%) of the 53 patients, at least one genetic alteration was identified. In 80% of these patients, the diagnosis was obtained (n = 11) or changed (n = 9), and thus genomic data affected therapy. The most frequent initial misdiagnosis was Ewing's sarcoma, instead of myxoid liposarcoma (FUS-DDDIT3), rhabdoid soft tissue tumor (SMARCB1), or angiomatoid fibrous histiocytoma (EWSR1-CREB1). In our series, two patients had a genetic alteration with an FDA-approved targeted therapy, and 30% had at least one potentially actionable alteration. NGS-based genomic studies are useful and feasible in diagnosis and clinical management of pediatric sarcomas. Genomic characterization of these rare and heterogeneous tumors also helps in the search for prognostic biomarkers and therapeutic opportunities.
Nacionales y Regionales
Título:
Alianza en Genómica Avanzada para el desarrollo de Terapias Avanzadas en Navarra (AGATA)
Código de expediente:
0011-1411-2020-000011
Investigador principal:
Felipe Luis Prósper Cardoso
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2020 GN PROYECTOS ESTRATEGICOS DE I+D 2020-2022
Fecha de inicio:
16/06/2020
Fecha fin:
30/11/2022
Importe concedido:
441.998,75€
Otros fondos:
-
Título:
Identificación y desarrollo de candidato inhibidor de HDAC6 como tratamiento frente al cáncer de colon (COLON-HDAC6)
Código de expediente:
0011-1411-2021-000097
Investigador principal:
Ana Gloria Gil Royo
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2021 GN PROYECTOS ESTRATEGICOS DE I+D 2021-2024
Fecha de inicio:
01/07/2021
Fecha fin:
31/12/2023
Importe concedido:
412.467,21€
Otros fondos:
-
Título:
Implantación del diagnóstico de la epilepsia y la migraña en Navarra (Geneurona)
Código de expediente:
0011-1411-2018-000054
Investigador principal:
Gorka Alkorta Aranburu
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2018 GN PROYECTOS ESTRATEGICOS DE I+D 2018-2020
Fecha de inicio:
01/04/2018
Fecha fin:
30/11/2020
Importe concedido:
557.099,44€
Otros fondos:
-
Título:
SEHOP-PENCIL study- Personalised Medicine for Cancer in Children in Spain Estrategia nacional para la implementación de la medicina personalizada en niños y adolescentes con cáncer A Spanish nation-wide strategy to implement personalised medicine in child
Código de expediente:
PMP21/00087
Investigador principal:
Ana Patiño García
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
2021 AES Medicina Personalizada
Fecha de inicio:
01/01/2022
Fecha fin:
31/12/2025
Importe concedido:
200.420,00€
Otros fondos:
-
Título:
Desarrollo y validación de paneles génicos en niños y adolescentes con cáncer: herramientas clínicas de diagnóstico, predicción y asesoramiento genético.
Código de expediente:
54/2018
Investigador principal:
Ana Patiño García
Financiador:
GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
Convocatoria:
2018 PROYECTOS DE I+D EN SALUD
Fecha de inicio:
01/01/2019
Fecha fin:
31/12/2020
Importe concedido:
49.352,25€
Otros fondos:
Fondos FEDER
Internacionales y Europeos
Título:
Red de cooperación transnacional para la mejora de los programas de salud de detección precoz de la hipoacusia infantil a través de herramientas genéticas innovadoras de diagnóstico
Investigador principal:
Manuel Jesús Manrique Rodríguez
Financiador:
INTERREG SUDOE
Convocatoria:
INTERREG SUDOE 2017
Fecha de inicio:
01/04/2018
Fecha fin:
31/03/2021
Importe concedido:
540.000,00€
Otros fondos:
Fondos FEDER
Otros (PIUNA, fundaciones, contratos…)
Título:
GENETIC SCREENING IN CHILDHOOD HEARING LOSS
Investigador principal:
Manuel Jesús Manrique Rodríguez
Fecha de inicio:
10/01/2023
Fecha fin:
10/07/2024
Importe:
231.684,00€
Otros fondos:
-