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Identification of a Novel Missense Mutation of POLR3A Gene in a Cohort of Sicilian Patients with Leukodystrophy

Recessive mutations in the POLR3A gene cause POLR3-HLD (the second-most-common form of childhood-onset hypomyelinating leukodystrophy), a neurodegenerative disorder featuring deficient cerebral myelin formation. To date, more than 140 POLR3A (NM_007055.3) missense mutations are related to the pathog...

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Autores principales: Musumeci, Antonino, Calì, Francesco, Scuderi, Carmela, Vinci, Mirella, Vitello, Girolamo Aurelio, Musumeci, Sebastiano Antonino, Chiavetta, Valeria, Federico, Concetta, Amore, Greta, Saccone, Salvatore, Di Rosa, Gabriella, Nicotera, Antonio Gennaro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496502/
https://www.ncbi.nlm.nih.gov/pubmed/36140376
http://dx.doi.org/10.3390/biomedicines10092276
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author Musumeci, Antonino
Calì, Francesco
Scuderi, Carmela
Vinci, Mirella
Vitello, Girolamo Aurelio
Musumeci, Sebastiano Antonino
Chiavetta, Valeria
Federico, Concetta
Amore, Greta
Saccone, Salvatore
Di Rosa, Gabriella
Nicotera, Antonio Gennaro
author_facet Musumeci, Antonino
Calì, Francesco
Scuderi, Carmela
Vinci, Mirella
Vitello, Girolamo Aurelio
Musumeci, Sebastiano Antonino
Chiavetta, Valeria
Federico, Concetta
Amore, Greta
Saccone, Salvatore
Di Rosa, Gabriella
Nicotera, Antonio Gennaro
author_sort Musumeci, Antonino
collection PubMed
description Recessive mutations in the POLR3A gene cause POLR3-HLD (the second-most-common form of childhood-onset hypomyelinating leukodystrophy), a neurodegenerative disorder featuring deficient cerebral myelin formation. To date, more than 140 POLR3A (NM_007055.3) missense mutations are related to the pathogenesis of POLR3-related leukodystrophy and spastic ataxia. Herein, in a cohort of five families from Sicily (Italy), we detected two cases of patients affected by POLR3-related leukodystrophy, one due to a compound heterozygous mutation in the POLR3A gene, including a previously undescribed missense mutation (c.328A > G (p.Lys110Glu)). Our study used an in-house NGS gene panel comprising 41 known leukodystrophy genes. Successively, we used a predictive test supporting the missense mutation as causative of disease, thus this mutation can be considered “Likely Pathogenic” and could be as a new pathogenetic mutation of the POLR3A gene causing a severe form of POLR3-HLD.
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spelling pubmed-94965022022-09-23 Identification of a Novel Missense Mutation of POLR3A Gene in a Cohort of Sicilian Patients with Leukodystrophy Musumeci, Antonino Calì, Francesco Scuderi, Carmela Vinci, Mirella Vitello, Girolamo Aurelio Musumeci, Sebastiano Antonino Chiavetta, Valeria Federico, Concetta Amore, Greta Saccone, Salvatore Di Rosa, Gabriella Nicotera, Antonio Gennaro Biomedicines Article Recessive mutations in the POLR3A gene cause POLR3-HLD (the second-most-common form of childhood-onset hypomyelinating leukodystrophy), a neurodegenerative disorder featuring deficient cerebral myelin formation. To date, more than 140 POLR3A (NM_007055.3) missense mutations are related to the pathogenesis of POLR3-related leukodystrophy and spastic ataxia. Herein, in a cohort of five families from Sicily (Italy), we detected two cases of patients affected by POLR3-related leukodystrophy, one due to a compound heterozygous mutation in the POLR3A gene, including a previously undescribed missense mutation (c.328A > G (p.Lys110Glu)). Our study used an in-house NGS gene panel comprising 41 known leukodystrophy genes. Successively, we used a predictive test supporting the missense mutation as causative of disease, thus this mutation can be considered “Likely Pathogenic” and could be as a new pathogenetic mutation of the POLR3A gene causing a severe form of POLR3-HLD. MDPI 2022-09-14 /pmc/articles/PMC9496502/ /pubmed/36140376 http://dx.doi.org/10.3390/biomedicines10092276 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Musumeci, Antonino
Calì, Francesco
Scuderi, Carmela
Vinci, Mirella
Vitello, Girolamo Aurelio
Musumeci, Sebastiano Antonino
Chiavetta, Valeria
Federico, Concetta
Amore, Greta
Saccone, Salvatore
Di Rosa, Gabriella
Nicotera, Antonio Gennaro
Identification of a Novel Missense Mutation of POLR3A Gene in a Cohort of Sicilian Patients with Leukodystrophy
title Identification of a Novel Missense Mutation of POLR3A Gene in a Cohort of Sicilian Patients with Leukodystrophy
title_full Identification of a Novel Missense Mutation of POLR3A Gene in a Cohort of Sicilian Patients with Leukodystrophy
title_fullStr Identification of a Novel Missense Mutation of POLR3A Gene in a Cohort of Sicilian Patients with Leukodystrophy
title_full_unstemmed Identification of a Novel Missense Mutation of POLR3A Gene in a Cohort of Sicilian Patients with Leukodystrophy
title_short Identification of a Novel Missense Mutation of POLR3A Gene in a Cohort of Sicilian Patients with Leukodystrophy
title_sort identification of a novel missense mutation of polr3a gene in a cohort of sicilian patients with leukodystrophy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496502/
https://www.ncbi.nlm.nih.gov/pubmed/36140376
http://dx.doi.org/10.3390/biomedicines10092276
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