CLN7 disease: phenotypic and genotypic description of four cases of a Cordoba cohort
Abstract: CLN7 disease (OMIM # 610951), caused by variants in the MFSD8/CLN7 gene, belongs to the group of neuronal ceroid lipofuscinoses (NCL). It presents mainly as a late infantile phenotype, where the first symptoms (seizures, developmental regression) usually appear...
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| Autores principales: | , , , , , , , |
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| Formato: | Artículo revista |
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Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2021
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| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/35038 |
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I10-R327-article-35038 |
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ojs |
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Universidad Nacional de Córdoba |
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I-10 |
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R-327 |
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Revista de la Facultad de Ciencias Médicas de Córdoba |
| format |
Artículo revista |
| topic |
Neuronal Ceroid Lipofuscinoses GENOTYPE PHENOTYPE lipofuscinosis ceroideas neuronales GENOTIPO FENOTIPO |
| spellingShingle |
Neuronal Ceroid Lipofuscinoses GENOTYPE PHENOTYPE lipofuscinosis ceroideas neuronales GENOTIPO FENOTIPO Venier , AC Pesaola , F Cismondi , IA Guelbert , G De Paul , AL Grondona , E Guelbert , N Noher , I CLN7 disease: phenotypic and genotypic description of four cases of a Cordoba cohort |
| topic_facet |
Neuronal Ceroid Lipofuscinoses GENOTYPE PHENOTYPE lipofuscinosis ceroideas neuronales GENOTIPO FENOTIPO |
| author |
Venier , AC Pesaola , F Cismondi , IA Guelbert , G De Paul , AL Grondona , E Guelbert , N Noher , I |
| author_facet |
Venier , AC Pesaola , F Cismondi , IA Guelbert , G De Paul , AL Grondona , E Guelbert , N Noher , I |
| author_sort |
Venier , AC |
| title |
CLN7 disease: phenotypic and genotypic description of four cases of a Cordoba cohort |
| title_short |
CLN7 disease: phenotypic and genotypic description of four cases of a Cordoba cohort |
| title_full |
CLN7 disease: phenotypic and genotypic description of four cases of a Cordoba cohort |
| title_fullStr |
CLN7 disease: phenotypic and genotypic description of four cases of a Cordoba cohort |
| title_full_unstemmed |
CLN7 disease: phenotypic and genotypic description of four cases of a Cordoba cohort |
| title_sort |
cln7 disease: phenotypic and genotypic description of four cases of a cordoba cohort |
| description |
Abstract:
CLN7 disease (OMIM # 610951), caused by variants in the MFSD8/CLN7 gene, belongs to the group of neuronal ceroid lipofuscinoses (NCL). It presents mainly as a late infantile phenotype, where the first symptoms (seizures, developmental regression) usually appear between 1.5 and 6 years, followed by rapid psychomotor deterioration, behavioral changes, myoclonus, speech disorders, occasional loss of vision, and premature death. Due to the low frequency and non-specificity of symptoms, it can be confused with the most common form of NCL, CLN2 (caused by variants in the TPP1/CLN2 gene). Therefore, genomic analysis is necessary to arrive at the diagnosis, thus determining which gene is affected. In the present study, the phenotype and genotype of four suspected NCL cases in a Cordoba cohort, and their consequent confirmation among NCL variants, are analyzed.
Those responsible for the children signed an informed consent approved by CIEIS-Polo Hospitalario from the Cordoba province. Two girls and two boys developed seizures, intellectual and speech retardation, and progressive psychomotor impairment from 3-4 years of age. The boys showed behavioral changes and visual failures as well. All showed mild to severe cerebellar atrophy with compromise of the white matter. NCL was suspected, and CLN1 and CLN2 diseases were excluded by enzymology. Genetic analysis revealed DNA variants in the MFSD8/CLN7 gene. The pathogenic variant E3 c.103C>T, p.Arg35* was observed in homozygous state in one girl and one boy, while in compound heterozygosity with the pathogenic variant I9 c.863+1G>A in the other boy; and the variants E13 c.1394G>A, p.Arg465Gln (pathogenic) and I9 c.863+4A>G (possibly pathogenic) were found in compound heterozygosis in the other girl. The pathogenicity of these variants was evaluated by bioinformatics means, bibliography and public databases.
The importance of genomic analysis is emphasized when non-specific progressive neurological symptoms are present and NCL is suspected, highlighting in this work the confirmation of four CLN7 cases in a cohort from Cordoba. Precise and early diagnosis allows predicting the evolution of the patient and a correct therapeutic approach. No author declares conflicts of interest. |
| publisher |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología |
| publishDate |
2021 |
| url |
https://revistas.unc.edu.ar/index.php/med/article/view/35038 |
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I10-R327-article-350382024-04-15T16:19:09Z CLN7 disease: phenotypic and genotypic description of four cases of a Cordoba cohort Enfermedad CLN7: descripción fenotípica y genotípica de cuatro casos de una cohorte de Córdoba Venier , AC Pesaola , F Cismondi , IA Guelbert , G De Paul , AL Grondona , E Guelbert , N Noher , I Neuronal Ceroid Lipofuscinoses GENOTYPE PHENOTYPE lipofuscinosis ceroideas neuronales GENOTIPO FENOTIPO Abstract: CLN7 disease (OMIM # 610951), caused by variants in the MFSD8/CLN7 gene, belongs to the group of neuronal ceroid lipofuscinoses (NCL). It presents mainly as a late infantile phenotype, where the first symptoms (seizures, developmental regression) usually appear between 1.5 and 6 years, followed by rapid psychomotor deterioration, behavioral changes, myoclonus, speech disorders, occasional loss of vision, and premature death. Due to the low frequency and non-specificity of symptoms, it can be confused with the most common form of NCL, CLN2 (caused by variants in the TPP1/CLN2 gene). Therefore, genomic analysis is necessary to arrive at the diagnosis, thus determining which gene is affected. In the present study, the phenotype and genotype of four suspected NCL cases in a Cordoba cohort, and their consequent confirmation among NCL variants, are analyzed. Those responsible for the children signed an informed consent approved by CIEIS-Polo Hospitalario from the Cordoba province. Two girls and two boys developed seizures, intellectual and speech retardation, and progressive psychomotor impairment from 3-4 years of age. The boys showed behavioral changes and visual failures as well. All showed mild to severe cerebellar atrophy with compromise of the white matter. NCL was suspected, and CLN1 and CLN2 diseases were excluded by enzymology. Genetic analysis revealed DNA variants in the MFSD8/CLN7 gene. The pathogenic variant E3 c.103C>T, p.Arg35* was observed in homozygous state in one girl and one boy, while in compound heterozygosity with the pathogenic variant I9 c.863+1G>A in the other boy; and the variants E13 c.1394G>A, p.Arg465Gln (pathogenic) and I9 c.863+4A>G (possibly pathogenic) were found in compound heterozygosis in the other girl. The pathogenicity of these variants was evaluated by bioinformatics means, bibliography and public databases. The importance of genomic analysis is emphasized when non-specific progressive neurological symptoms are present and NCL is suspected, highlighting in this work the confirmation of four CLN7 cases in a cohort from Cordoba. Precise and early diagnosis allows predicting the evolution of the patient and a correct therapeutic approach. No author declares conflicts of interest. Resumen: La enfermedad CLN7 (OMIM #610951), causada por variantes en el gen MFSD8/CLN7, pertenece al grupo de las lipofuscinosis ceroideas neuronales (LCN). Se presenta principalmente como un fenotipo infantil tardío, donde los primeros síntomas (convulsiones, regresión del desarrollo) suelen aparecer entre los 1,5 y 6 años, seguidos de deterioro psicomotor rápido, cambios de comportamiento, mioclonías, trastornos del habla, ocasional pérdida de la visión, y muerte prematura. Dada la baja frecuencia e inespecificidad de los síntomas puede confundirse con la forma más común de LCN, CLN2 (causada por variantes en el gen TPP1/CLN2). Por ende, para arribar al diagnóstico es necesario el análisis genómico, determinando así cuál es el gen que se encuentra afectado. En el presente trabajo se analizan el fenotipo y genotipo de cuatro casos sospechados de padecer LCN en una cohorte de Córdoba, y su consecuente confirmación entre las variantes de LCN. Los responsables de los niños firmaron un consentimiento informado aprobado por el CIEIS-Polo Hospitalario de la Provincia de Córdoba. Dos niñas y dos niños desarrollaron convulsiones, retraso intelectual y del habla, y deterioro psicomotor progresivo desde los 3-4 años de vida. Los varones mostraron cambios comportamentales y fallas visuales. Todos presentaron atrofia cerebelosa leve a severa con compromiso de la sustancia blanca. Se sospecha LCN y se descartan CLN1 y CLN2 por enzimología. El análisis genético reveló mutaciones en el gen MFSD8/CLN7. La variante patogénica E3 c.103C>T, p.Arg35* se presentó en homocigosis en una de las niñas y uno de los niños, mientras que, en el otro niño, en heterocigosis compuesta con I9 c.863+1G>A (patogénica); y en la otra niña las variantes E13 c.1394G>A, p.Arg465Gln (patogénica) e I9 c.863+4A>G (posiblemente patogénica) en heterocigosis. La patogenicidad de las variantes halladas fue evaluada por medios bioinformáticos, bibliografía y bases de datos públicas. Se enfatiza la importancia del análisis genómico cuando se presentan síntomas neurológicos progresivos poco específicos y se sospecha de LCN, destacándose en este trabajo la confirmación de cuatro casos CLN7 en una cohorte de Córdoba. El diagnóstico preciso y temprano permite predecir la evolución del paciente y un correcto abordaje terapéutico. Ningún autor declara conflictos de intereses. Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2021-10-12 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion texto texto texto https://revistas.unc.edu.ar/index.php/med/article/view/35038 Revista de la Facultad de Ciencias Médicas de Córdoba.; Vol. 78 No. Suplemento (2021): Suplemento JIC XXII Revista de la Facultad de Ciencias Médicas de Córdoba; Vol. 78 Núm. Suplemento (2021): Suplemento JIC XXII Revista da Faculdade de Ciências Médicas de Córdoba; v. 78 n. Suplemento (2021): Suplemento JIC XXII 1853-0605 0014-6722 http://creativecommons.org/licenses/by-nc/4.0 |