Por favor, use este identificador para citar o enlazar este ítem: https://hdl.handle.net/20.500.12008/56063

Título:

Two compound heterozygous variants in the CLN8 gene are responsible for neuronal cereidolipofuscinoses disorder in a child: a case report

Otros títulos:

Coordinador:

Director:

Compilador:

Autor:

Baltar, Federico
Simoes, Camila
Garagorry, Francisco
Graña, Martín
Rodríguez, Soledad
Aunchayna, María Haydée
Tapié, Alejandra
Cerisola, Alfredo
González, Gabriel
Naya, Hugo
Spangenberg, Lucía
Raggio, Víctor

Tutor:

Tipo de documento:

Artículo

Editor:

Palabras clave:

Genomics
Whole genome sequencing
Neurological disorders
Neurodegeneration
CLN8
Ceroid lipofuscinosis

Descriptores:

LIPOFUSCINOSIS CEROIDEAS NEURONALES
MUTACIÓN
GENÉTICA
GENÓMICA
NIÑO
HUMANOS
ENFERMEDADES DEL SISTEMA NERVIOSO
ENFERMEDADES NEURODEGENERATIVAS
ENFERMEDADES RARAS

Año de publicación:

2024

Contenido:

Resumen:

Background Neuronal Ceroid Lipofuscinosis (NCL) disorders, recognized as the primary cause of childhood dementia globally, constitute a spectrum of genetic abnormalities. CLN8, a subtype within NCL, is characterized by cognitive decline, motor impairment, and visual deterioration. This study focuses on an atypical case with congenital onset and a remarkably slow disease progression. Methods Whole-genome sequencing at 30× coverage was employed as part of a national genomics program to investigate the genetic underpinnings of rare diseases. This genomic approach aimed to challenge established classifications (vLINCL and EPMR) and explore the presence of a continuous phenotypic spectrum associated with CLN8. Results The whole-genome sequencing revealed two novel likely pathogenic mutations in the CLN8 gene on chromosome 8p23.3. These mutations were not previously associated with CLN8-related NCL. Contrary to established classifications (vLINCL and EPMR), our findings suggest a continuous phenotypic spectrum associated with CLN8. Pathological subcellular markers further validated the genomic insights. Discussion The identification of two previously undescribed likely pathogenic CLN8 gene mutations challenges traditional classifications and highlights a more nuanced phenotypic spectrum associated with CLN8. Our findings underscore the significance of genetic modifiers and interactions with unrelated genes in shaping variable phenotypic outcomes. The inclusion of pathological subcellular markers further strengthens the validity of our genomic insights. This research enhances our understanding of CLN8 disorders, emphasizing the need for comprehensive genomic analyses to elucidate the complexity of phenotypic presentations and guide tailored therapeutic strategies. The identification of new likely pathogenic mutations underscores the dynamic nature of CLN8-related NCL and the importance of individualized approaches to patient management.

Descripción:

metadata.articulos.dc.description.uri:

Editorial:

Frontiers Media

EN:

Frontiers in Pediatrics. 2024;12

Financiadores:

Citación:

Baltar F, Simoes C, Garagorry F y otros. Two compound heterozygous variants in the CLN8 gene are responsible for neuronal cereidolipofuscinoses disorder in a child: a case report. Frontiers in Pediatrics [en línea]. 2024;12. 7 p.

Citación:

metadata.articulos.cc.license.name:

ISBN:

e-ISBN:

ISSN:

ISMN:

Otros identificadores:

Cobertura geográfica:

Cobertura temporal:

Departamento académico:

Grupo de investigación:

Licencia:

Licencia Creative Commons Atribución (CC - By 4.0)

Colecciones:

Publicaciones Académicas y Científicas
FicherosDescripciónTamañoFormato
Two compound heterozygous variants in the CLN8 gene.pdf Two compound heterozygous variants in the CLN8 gene 3.59 MB Adobe PDF
Mostrar el registro Dublin Core completo del ítem