Two compound heterozygous variants in the CLN8 gene are responsible for neuronal cereidolipofuscinoses disorder in a child: a case report
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.
| 2024 | |
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Banco Iberomericano de Desarrollo Fondo para la Convergencia Estructural del Mercosur Agencia Nacional de Investigación e Innovación |
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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 |
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| Inglés | |
| Institut Pasteur de Montevideo | |
| IPMON en REDI | |
| https://hdl.handle.net/20.500.12381/4062 | |
| Acceso abierto | |
| Reconocimiento 4.0 Internacional. (CC BY) |
| _version_ | 1879737345189609472 |
|---|---|
| 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 |