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

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

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.

Detalles Bibliográficos
2024
Banco Iberomericano de Desarrollo
Fondo para la Convergencia Estructural del Mercosur
Agencia Nacional de Investigación e Innovación
genómica médica
Ciencias Naturales y Exactas
Ciencias de la Computación e Información
Ciencias de la Información y Bioinformática
Ciencias Médicas y de la Salud
Medicina Básica
Genética Humana
Inglés
Institut Pasteur de Montevideo
IPMON en REDI
https://hdl.handle.net/20.500.12381/4062
Acceso abierto
Reconocimiento 4.0 Internacional. (CC BY)
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author Baltar, Federico
author2 Simoes, Camila
Garagorry, Francisco
Graña, Martín
Rodríguez, Soledad
Aunchayna, María Haydée
Tapié, Alejandra
Cerisola, Alfredo
González, Gabriel
Naya, Hugo
Spangenberg, Lucía
Raggio, Víctor
author2_role author
author
author
author
author
author
author
author
author
author
author
author_facet 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
author_role author
bitstream.checksum.fl_str_mv 710ccfef5cb01d54b75d1d847d6b6b7b
2232ef04786cd1726231b498ffeba5ad
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
bitstream.url.fl_str_mv https://redi.anii.org.uy/jspui/bitstream/20.500.12381/4062/2/license.txt
https://redi.anii.org.uy/jspui/bitstream/20.500.12381/4062/1/fped-12-1379254.pdf
collection IPMON en REDI
dc.creator.none.fl_str_mv 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
dc.date.accessioned.none.fl_str_mv 2025-06-11T17:49:58Z
dc.date.available.none.fl_str_mv 2025-06-11T17:49:58Z
dc.date.issued.none.fl_str_mv 2024-05-01
dc.description.abstract.none.fl_txt_mv 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.
dc.description.sponsorship.none.fl_txt_mv Banco Iberomericano de Desarrollo
Fondo para la Convergencia Estructural del Mercosur
Agencia Nacional de Investigación e Innovación
dc.identifier.anii.es.fl_str_mv FSS_X_2022_1_173209
dc.identifier.doi.none.fl_str_mv 10.3389/fped.2024.1379254
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12381/4062
dc.language.iso.none.fl_str_mv eng
dc.publisher.es.fl_str_mv Frontiers
dc.rights.*.fl_str_mv Acceso abierto
dc.rights.license.none.fl_str_mv Reconocimiento 4.0 Internacional. (CC BY)
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
dc.source.es.fl_str_mv Frontiers in Pediatrics
dc.source.none.fl_str_mv reponame:IPMON en REDI
instname:Institut Pasteur de Montevideo
instacron:Institut Pasteur de Montevideo
dc.subject.anii.none.fl_str_mv Ciencias Naturales y Exactas
Ciencias de la Computación e Información
Ciencias de la Información y Bioinformática
Ciencias Médicas y de la Salud
Medicina Básica
Genética Humana
dc.subject.es.fl_str_mv genómica médica
dc.title.none.fl_str_mv Two compound heterozygous variants in the CLN8 gene are responsible for neuronal cereidolipofuscinoses disorder in a child: a case report
dc.type.es.fl_str_mv Artículo
dc.type.none.fl_str_mv info:eu-repo/semantics/article
dc.type.version.es.fl_str_mv Publicado
dc.type.version.none.fl_str_mv info:eu-repo/semantics/publishedVersion
description 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.
eu_rights_str_mv openAccess
format article
id IPMON_3f7cfd6db5f69e42b4f2758d41953d1d
identifier_str_mv FSS_X_2022_1_173209
10.3389/fped.2024.1379254
instacron_str Institut Pasteur de Montevideo
institution Institut Pasteur de Montevideo
instname_str Institut Pasteur de Montevideo
language eng
network_acronym_str IPMON
network_name_str IPMON en REDI
oai_identifier_str oai:redi.anii.org.uy:20.500.12381/4062
publishDate 2024
reponame_str IPMON en REDI
repository.mail.fl_str_mv msarroca@pasteur.edu.uy
repository.name.fl_str_mv IPMON en REDI - Institut Pasteur de Montevideo
repository_id_str 9421_2
rights_invalid_str_mv Reconocimiento 4.0 Internacional. (CC BY)
Acceso abierto
spelling Reconocimiento 4.0 Internacional. (CC BY)Acceso abiertoinfo:eu-repo/semantics/openAccess2025-06-11T17:49:58Z2025-06-11T17:49:58Z2024-05-01https://hdl.handle.net/20.500.12381/4062FSS_X_2022_1_17320910.3389/fped.2024.1379254Background 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.Banco Iberomericano de DesarrolloFondo para la Convergencia Estructural del MercosurAgencia Nacional de Investigación e InnovaciónengFrontiersFrontiers in Pediatricsreponame:IPMON en REDIinstname:Institut Pasteur de Montevideoinstacron:Institut Pasteur de Montevideogenómica médicaCiencias Naturales y ExactasCiencias de la Computación e InformaciónCiencias de la Información y BioinformáticaCiencias Médicas y de la SaludMedicina BásicaGenética HumanaTwo compound heterozygous variants in the CLN8 gene are responsible for neuronal cereidolipofuscinoses disorder in a child: a case reportArtículoPublicadoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFacultad de Medicina, Universidad de la República, Montevideo, UruguayInstitut Pasteur de Montevideo, Montevideo, UruguayHospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, UruguayFacultad de Agronomía, Universidad de la República, Montevideo, Uruguay//Ciencias Naturales y Exactas/Ciencias de la Computación e Información/Ciencias de la Información y Bioinformática//Ciencias Médicas y de la Salud/Medicina Básica/Genética HumanaBaltar, FedericoSimoes, CamilaGaragorry, FranciscoGraña, MartínRodríguez, SoledadAunchayna, María HaydéeTapié, AlejandraCerisola, AlfredoGonzález, GabrielNaya, HugoSpangenberg, LucíaRaggio, VíctorLICENSElicense.txtlicense.txttext/plain; charset=utf-85124https://redi.anii.org.uy/jspui/bitstream/20.500.12381/4062/2/license.txt710ccfef5cb01d54b75d1d847d6b6b7bMD52ORIGINALfped-12-1379254.pdffped-12-1379254.pdfapplication/pdf1864657https://redi.anii.org.uy/jspui/bitstream/20.500.12381/4062/1/fped-12-1379254.pdf2232ef04786cd1726231b498ffeba5adMD5120.500.12381/40622025-06-11 14:49:59.588oai:redi.anii.org.uy:20.500.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://hdl.handle.net/20.500.12381/575Organismo científico-tecnológicohttps://pasteur.uy/https://redi.anii.org.uy/oai/requestmsarroca@pasteur.edu.uyUruguayopendoar:9421_22025-06-11T17:49:59IPMON en REDI - Institut Pasteur de Montevideofalse
spellingShingle Two compound heterozygous variants in the CLN8 gene are responsible for neuronal cereidolipofuscinoses disorder in a child: a case report
Baltar, Federico
genómica médica
Ciencias Naturales y Exactas
Ciencias de la Computación e Información
Ciencias de la Información y Bioinformática
Ciencias Médicas y de la Salud
Medicina Básica
Genética Humana
status_str publishedVersion
title Two compound heterozygous variants in the CLN8 gene are responsible for neuronal cereidolipofuscinoses disorder in a child: a case report
title_full Two compound heterozygous variants in the CLN8 gene are responsible for neuronal cereidolipofuscinoses disorder in a child: a case report
title_fullStr Two compound heterozygous variants in the CLN8 gene are responsible for neuronal cereidolipofuscinoses disorder in a child: a case report
title_full_unstemmed Two compound heterozygous variants in the CLN8 gene are responsible for neuronal cereidolipofuscinoses disorder in a child: a case report
title_short Two compound heterozygous variants in the CLN8 gene are responsible for neuronal cereidolipofuscinoses disorder in a child: a case report
title_sort Two compound heterozygous variants in the CLN8 gene are responsible for neuronal cereidolipofuscinoses disorder in a child: a case report
topic genómica médica
Ciencias Naturales y Exactas
Ciencias de la Computación e Información
Ciencias de la Información y Bioinformática
Ciencias Médicas y de la Salud
Medicina Básica
Genética Humana
url https://hdl.handle.net/20.500.12381/4062