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Novel likely disease-causing CLN5 variants identified in Pakistani patients with neuronal ceroid lipofuscinosis
BACKGROUND: Neuronal ceroid lipofuscinosis (NCL) is a hereditary lysosomal storage disease with progressive brain neurodegeneration. Mutations in ceroid lipofuscinosis neuronal protein 5 (CLN5) cause CLN5 disease, a severe condition characterized by seizures, visual failure, motor decline, and progr...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306150/ https://www.ncbi.nlm.nih.gov/pubmed/32302805 http://dx.doi.org/10.1016/j.jns.2020.116826 |
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author | Azad, Beenish Efthymiou, Stephanie Sultan, Tipu Scala, Marcello Alvi, Javeria Raza Neuray, Caroline Dominik, Natalia Gul, Asma Houlden, Henry |
author_facet | Azad, Beenish Efthymiou, Stephanie Sultan, Tipu Scala, Marcello Alvi, Javeria Raza Neuray, Caroline Dominik, Natalia Gul, Asma Houlden, Henry |
author_sort | Azad, Beenish |
collection | PubMed |
description | BACKGROUND: Neuronal ceroid lipofuscinosis (NCL) is a hereditary lysosomal storage disease with progressive brain neurodegeneration. Mutations in ceroid lipofuscinosis neuronal protein 5 (CLN5) cause CLN5 disease, a severe condition characterized by seizures, visual failure, motor decline, and progressive cognitive deterioration. This study aimed to identify causative gene variants in Pakistani consanguineous families diagnosed with NCL. METHODS: After a thorough clinical and neuroradiological characterization, whole exome sequencing (WES) was performed in 3 patients from 2 unrelated families. Segregation analysis was subsequently performed through Sanger sequencing ANALYSIS: WES led to the identification of the 2 novel homozygous variants c.925_926del, (p.Leu309AlafsTer4) and c.477 T > C, (p.Cys159Arg). CONCLUSION: In this study, we report two novel CLN5 cases in the Punjab region of Pakistan. Our observations will help clinicians observe and compare common and unique clinical features of NCL patients, further improving our current understanding of NCL. |
format | Online Article Text |
id | pubmed-7306150 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-73061502020-07-15 Novel likely disease-causing CLN5 variants identified in Pakistani patients with neuronal ceroid lipofuscinosis Azad, Beenish Efthymiou, Stephanie Sultan, Tipu Scala, Marcello Alvi, Javeria Raza Neuray, Caroline Dominik, Natalia Gul, Asma Houlden, Henry J Neurol Sci Article BACKGROUND: Neuronal ceroid lipofuscinosis (NCL) is a hereditary lysosomal storage disease with progressive brain neurodegeneration. Mutations in ceroid lipofuscinosis neuronal protein 5 (CLN5) cause CLN5 disease, a severe condition characterized by seizures, visual failure, motor decline, and progressive cognitive deterioration. This study aimed to identify causative gene variants in Pakistani consanguineous families diagnosed with NCL. METHODS: After a thorough clinical and neuroradiological characterization, whole exome sequencing (WES) was performed in 3 patients from 2 unrelated families. Segregation analysis was subsequently performed through Sanger sequencing ANALYSIS: WES led to the identification of the 2 novel homozygous variants c.925_926del, (p.Leu309AlafsTer4) and c.477 T > C, (p.Cys159Arg). CONCLUSION: In this study, we report two novel CLN5 cases in the Punjab region of Pakistan. Our observations will help clinicians observe and compare common and unique clinical features of NCL patients, further improving our current understanding of NCL. Elsevier 2020-07-15 /pmc/articles/PMC7306150/ /pubmed/32302805 http://dx.doi.org/10.1016/j.jns.2020.116826 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Azad, Beenish Efthymiou, Stephanie Sultan, Tipu Scala, Marcello Alvi, Javeria Raza Neuray, Caroline Dominik, Natalia Gul, Asma Houlden, Henry Novel likely disease-causing CLN5 variants identified in Pakistani patients with neuronal ceroid lipofuscinosis |
title | Novel likely disease-causing CLN5 variants identified in Pakistani patients with neuronal ceroid lipofuscinosis |
title_full | Novel likely disease-causing CLN5 variants identified in Pakistani patients with neuronal ceroid lipofuscinosis |
title_fullStr | Novel likely disease-causing CLN5 variants identified in Pakistani patients with neuronal ceroid lipofuscinosis |
title_full_unstemmed | Novel likely disease-causing CLN5 variants identified in Pakistani patients with neuronal ceroid lipofuscinosis |
title_short | Novel likely disease-causing CLN5 variants identified in Pakistani patients with neuronal ceroid lipofuscinosis |
title_sort | novel likely disease-causing cln5 variants identified in pakistani patients with neuronal ceroid lipofuscinosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306150/ https://www.ncbi.nlm.nih.gov/pubmed/32302805 http://dx.doi.org/10.1016/j.jns.2020.116826 |
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