“Atypical” Phenotypes of Neuronal Ceroid Lipofuscinosis: The Argentine Experience in the Genomic Era
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Journal of Inborn Errors of Metabolism and Screening |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942021000100308 |
Resumo: | ABSTRACT Neuronal Ceroid Lipofuscinosis (NCL) refers to a group of inherited lysosomal storage disorders characterized by the intracellular accumulation of ceroid-lipofuscin compounds and neurodegeneration. Fourteen genes are currently recognized with disease-causing DNA variants: PPT1/CLN1, TPP1/CLN2, CLN3, DNAJC5/CLN4, CLN5, CLN6, MFSD8/CLN7, CLN8, CTSD/CN10, GRN/CLN11, ATP13A2/CLN12, CTSF/CLN13, KCTD7/CLN14, TBCK/CLN15. In the frame of the Cordoba cohort, we studied N=51 cases. The aim of this paper is the observational and retrospective analysis of the “atypical” phenotypes. PCR-Sanger sequencing and/or massive exome sequencing were used as a screening methodology. One CLN1 subject showed an atypical prolonged (P) phenotype with null PPT1 activity and a heterozygous compound genotype: E5 c.451C>T, p.Arg151*/g.6302T>G (I3 c.363-3T>G). Other 11 CLN2 individuals (except one girl) showed TPP1 activity decreased to around 10% of the minimum value of the reference interval in leukocytes and saliva. The DNA variants E7 c.827A>T, p.Asp276Val and I7 c.887-10A>G were the most prevalent. One CLN8 individual showed an atypical congenital phenotype with a heterozygous combination of DNA variants: E2 c.1A>G, p.?/E3 c.792C>G, p.Asn264Lys. Massive sequencing was installed as a screening methodology for the precision diagnosis of atypical CLN1, CLN2, and CLN8 phenotypes. A genetic/phenotypic local registry is under construction. |
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“Atypical” Phenotypes of Neuronal Ceroid Lipofuscinosis: The Argentine Experience in the Genomic EraNeuronal CeroidLipofuscinosisGenomicsCLN1CLN2CLN8Atypical PhenotypesABSTRACT Neuronal Ceroid Lipofuscinosis (NCL) refers to a group of inherited lysosomal storage disorders characterized by the intracellular accumulation of ceroid-lipofuscin compounds and neurodegeneration. Fourteen genes are currently recognized with disease-causing DNA variants: PPT1/CLN1, TPP1/CLN2, CLN3, DNAJC5/CLN4, CLN5, CLN6, MFSD8/CLN7, CLN8, CTSD/CN10, GRN/CLN11, ATP13A2/CLN12, CTSF/CLN13, KCTD7/CLN14, TBCK/CLN15. In the frame of the Cordoba cohort, we studied N=51 cases. The aim of this paper is the observational and retrospective analysis of the “atypical” phenotypes. PCR-Sanger sequencing and/or massive exome sequencing were used as a screening methodology. One CLN1 subject showed an atypical prolonged (P) phenotype with null PPT1 activity and a heterozygous compound genotype: E5 c.451C>T, p.Arg151*/g.6302T>G (I3 c.363-3T>G). Other 11 CLN2 individuals (except one girl) showed TPP1 activity decreased to around 10% of the minimum value of the reference interval in leukocytes and saliva. The DNA variants E7 c.827A>T, p.Asp276Val and I7 c.887-10A>G were the most prevalent. One CLN8 individual showed an atypical congenital phenotype with a heterozygous combination of DNA variants: E2 c.1A>G, p.?/E3 c.792C>G, p.Asn264Lys. Massive sequencing was installed as a screening methodology for the precision diagnosis of atypical CLN1, CLN2, and CLN8 phenotypes. A genetic/phenotypic local registry is under construction.Latin American Society Inborn Errors and Neonatal Screening (SLEIMPN); Instituto Genética para Todos (IGPT)2021-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942021000100308Journal of Inborn Errors of Metabolism and Screening v.9 2021reponame:Journal of Inborn Errors of Metabolism and Screeninginstname:Instituto Genética para Todos (IGPT)instacron:IGPT10.1590/2326-4594-jiems-2021-0009info:eu-repo/semantics/openAccessPesaola,FavioGuelbert,GuillermoVenier,Ana ClaraCismondi,Inés AdrianaBecerra,AdrianaVazquez,Juan Carlos G.Fernandez,ElmerDe Paul,Ana LuciaGuelbert,NorbertoNoher,Inéseng2021-05-03T00:00:00Zoai:scielo:S2326-45942021000100308Revistahttp://jiems-journal.org/ONGhttps://old.scielo.br/oai/scielo-oai.phpjiems@jiems-journal.org||rgiugliani@hcpa.edu.br2326-45942326-4594opendoar:2021-05-03T00:00Journal of Inborn Errors of Metabolism and Screening - Instituto Genética para Todos (IGPT)false |
dc.title.none.fl_str_mv |
“Atypical” Phenotypes of Neuronal Ceroid Lipofuscinosis: The Argentine Experience in the Genomic Era |
title |
“Atypical” Phenotypes of Neuronal Ceroid Lipofuscinosis: The Argentine Experience in the Genomic Era |
spellingShingle |
“Atypical” Phenotypes of Neuronal Ceroid Lipofuscinosis: The Argentine Experience in the Genomic Era Pesaola,Favio Neuronal CeroidLipofuscinosis Genomics CLN1 CLN2 CLN8 Atypical Phenotypes |
title_short |
“Atypical” Phenotypes of Neuronal Ceroid Lipofuscinosis: The Argentine Experience in the Genomic Era |
title_full |
“Atypical” Phenotypes of Neuronal Ceroid Lipofuscinosis: The Argentine Experience in the Genomic Era |
title_fullStr |
“Atypical” Phenotypes of Neuronal Ceroid Lipofuscinosis: The Argentine Experience in the Genomic Era |
title_full_unstemmed |
“Atypical” Phenotypes of Neuronal Ceroid Lipofuscinosis: The Argentine Experience in the Genomic Era |
title_sort |
“Atypical” Phenotypes of Neuronal Ceroid Lipofuscinosis: The Argentine Experience in the Genomic Era |
author |
Pesaola,Favio |
author_facet |
Pesaola,Favio Guelbert,Guillermo Venier,Ana Clara Cismondi,Inés Adriana Becerra,Adriana Vazquez,Juan Carlos G. Fernandez,Elmer De Paul,Ana Lucia Guelbert,Norberto Noher,Inés |
author_role |
author |
author2 |
Guelbert,Guillermo Venier,Ana Clara Cismondi,Inés Adriana Becerra,Adriana Vazquez,Juan Carlos G. Fernandez,Elmer De Paul,Ana Lucia Guelbert,Norberto Noher,Inés |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Pesaola,Favio Guelbert,Guillermo Venier,Ana Clara Cismondi,Inés Adriana Becerra,Adriana Vazquez,Juan Carlos G. Fernandez,Elmer De Paul,Ana Lucia Guelbert,Norberto Noher,Inés |
dc.subject.por.fl_str_mv |
Neuronal CeroidLipofuscinosis Genomics CLN1 CLN2 CLN8 Atypical Phenotypes |
topic |
Neuronal CeroidLipofuscinosis Genomics CLN1 CLN2 CLN8 Atypical Phenotypes |
description |
ABSTRACT Neuronal Ceroid Lipofuscinosis (NCL) refers to a group of inherited lysosomal storage disorders characterized by the intracellular accumulation of ceroid-lipofuscin compounds and neurodegeneration. Fourteen genes are currently recognized with disease-causing DNA variants: PPT1/CLN1, TPP1/CLN2, CLN3, DNAJC5/CLN4, CLN5, CLN6, MFSD8/CLN7, CLN8, CTSD/CN10, GRN/CLN11, ATP13A2/CLN12, CTSF/CLN13, KCTD7/CLN14, TBCK/CLN15. In the frame of the Cordoba cohort, we studied N=51 cases. The aim of this paper is the observational and retrospective analysis of the “atypical” phenotypes. PCR-Sanger sequencing and/or massive exome sequencing were used as a screening methodology. One CLN1 subject showed an atypical prolonged (P) phenotype with null PPT1 activity and a heterozygous compound genotype: E5 c.451C>T, p.Arg151*/g.6302T>G (I3 c.363-3T>G). Other 11 CLN2 individuals (except one girl) showed TPP1 activity decreased to around 10% of the minimum value of the reference interval in leukocytes and saliva. The DNA variants E7 c.827A>T, p.Asp276Val and I7 c.887-10A>G were the most prevalent. One CLN8 individual showed an atypical congenital phenotype with a heterozygous combination of DNA variants: E2 c.1A>G, p.?/E3 c.792C>G, p.Asn264Lys. Massive sequencing was installed as a screening methodology for the precision diagnosis of atypical CLN1, CLN2, and CLN8 phenotypes. A genetic/phenotypic local registry is under construction. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-01-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942021000100308 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942021000100308 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/2326-4594-jiems-2021-0009 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Latin American Society Inborn Errors and Neonatal Screening (SLEIMPN); Instituto Genética para Todos (IGPT) |
publisher.none.fl_str_mv |
Latin American Society Inborn Errors and Neonatal Screening (SLEIMPN); Instituto Genética para Todos (IGPT) |
dc.source.none.fl_str_mv |
Journal of Inborn Errors of Metabolism and Screening v.9 2021 reponame:Journal of Inborn Errors of Metabolism and Screening instname:Instituto Genética para Todos (IGPT) instacron:IGPT |
instname_str |
Instituto Genética para Todos (IGPT) |
instacron_str |
IGPT |
institution |
IGPT |
reponame_str |
Journal of Inborn Errors of Metabolism and Screening |
collection |
Journal of Inborn Errors of Metabolism and Screening |
repository.name.fl_str_mv |
Journal of Inborn Errors of Metabolism and Screening - Instituto Genética para Todos (IGPT) |
repository.mail.fl_str_mv |
jiems@jiems-journal.org||rgiugliani@hcpa.edu.br |
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1754732520248705024 |