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Severe Infantile Axonal Neuropathy with Respiratory Failure Caused by Novel Mutation in X-Linked LAS1L Gene

LAS1L encodes a nucleolar ribosomal biogenesis protein and is also a component of the Five Friends of Methylated CHTOP (5FMC) complex. Mutations in the LAS1L gene can be associated with Wilson–Turner syndrome (WTS) and, much more rarely, severe infantile hypotonia with respiratory failure. Here, we...

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Autores principales: Stembalska, Agnieszka, Rydzanicz, Małgorzata, Walas, Wojciech, Gasperowicz, Piotr, Pollak, Agnieszka, Pienkowski, Victor Murcia, Biela, Mateusz, Klaniewska, Magdalena, Gamrot, Zuzanna, Gronska, Ewa, Ploski, Rafal, Smigiel, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9142081/
https://www.ncbi.nlm.nih.gov/pubmed/35627110
http://dx.doi.org/10.3390/genes13050725
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author Stembalska, Agnieszka
Rydzanicz, Małgorzata
Walas, Wojciech
Gasperowicz, Piotr
Pollak, Agnieszka
Pienkowski, Victor Murcia
Biela, Mateusz
Klaniewska, Magdalena
Gamrot, Zuzanna
Gronska, Ewa
Ploski, Rafal
Smigiel, Robert
author_facet Stembalska, Agnieszka
Rydzanicz, Małgorzata
Walas, Wojciech
Gasperowicz, Piotr
Pollak, Agnieszka
Pienkowski, Victor Murcia
Biela, Mateusz
Klaniewska, Magdalena
Gamrot, Zuzanna
Gronska, Ewa
Ploski, Rafal
Smigiel, Robert
author_sort Stembalska, Agnieszka
collection PubMed
description LAS1L encodes a nucleolar ribosomal biogenesis protein and is also a component of the Five Friends of Methylated CHTOP (5FMC) complex. Mutations in the LAS1L gene can be associated with Wilson–Turner syndrome (WTS) and, much more rarely, severe infantile hypotonia with respiratory failure. Here, we present an eighteen-month old boy with a phenotype of spinal muscular atrophy with respiratory distress (SMARD). By applying WES, we identified a novel hemizygous synonymous variant in the LAS1L gene inherited from an unaffected mother (c.846G > C, p.Thr282=). We suggest that the identified variant impairs the RNA splicing process. Furthermore, we proved the absence of any coding regions by qPCR and sequencing cDNA using amplicon deep sequencing and Sanger sequencing methods. According to the SMARD phenotype, severe breathing problems causing respiratory insufficiency, hypotonia, and feeding difficulties were observed in our patient from the first days of life. Remarkably, our case is the second described patient with a SMARD-like phenotype due to a mutation in the LAS1L gene and the first with a variant impacting splicing.
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spelling pubmed-91420812022-05-28 Severe Infantile Axonal Neuropathy with Respiratory Failure Caused by Novel Mutation in X-Linked LAS1L Gene Stembalska, Agnieszka Rydzanicz, Małgorzata Walas, Wojciech Gasperowicz, Piotr Pollak, Agnieszka Pienkowski, Victor Murcia Biela, Mateusz Klaniewska, Magdalena Gamrot, Zuzanna Gronska, Ewa Ploski, Rafal Smigiel, Robert Genes (Basel) Case Report LAS1L encodes a nucleolar ribosomal biogenesis protein and is also a component of the Five Friends of Methylated CHTOP (5FMC) complex. Mutations in the LAS1L gene can be associated with Wilson–Turner syndrome (WTS) and, much more rarely, severe infantile hypotonia with respiratory failure. Here, we present an eighteen-month old boy with a phenotype of spinal muscular atrophy with respiratory distress (SMARD). By applying WES, we identified a novel hemizygous synonymous variant in the LAS1L gene inherited from an unaffected mother (c.846G > C, p.Thr282=). We suggest that the identified variant impairs the RNA splicing process. Furthermore, we proved the absence of any coding regions by qPCR and sequencing cDNA using amplicon deep sequencing and Sanger sequencing methods. According to the SMARD phenotype, severe breathing problems causing respiratory insufficiency, hypotonia, and feeding difficulties were observed in our patient from the first days of life. Remarkably, our case is the second described patient with a SMARD-like phenotype due to a mutation in the LAS1L gene and the first with a variant impacting splicing. MDPI 2022-04-21 /pmc/articles/PMC9142081/ /pubmed/35627110 http://dx.doi.org/10.3390/genes13050725 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 Case Report
Stembalska, Agnieszka
Rydzanicz, Małgorzata
Walas, Wojciech
Gasperowicz, Piotr
Pollak, Agnieszka
Pienkowski, Victor Murcia
Biela, Mateusz
Klaniewska, Magdalena
Gamrot, Zuzanna
Gronska, Ewa
Ploski, Rafal
Smigiel, Robert
Severe Infantile Axonal Neuropathy with Respiratory Failure Caused by Novel Mutation in X-Linked LAS1L Gene
title Severe Infantile Axonal Neuropathy with Respiratory Failure Caused by Novel Mutation in X-Linked LAS1L Gene
title_full Severe Infantile Axonal Neuropathy with Respiratory Failure Caused by Novel Mutation in X-Linked LAS1L Gene
title_fullStr Severe Infantile Axonal Neuropathy with Respiratory Failure Caused by Novel Mutation in X-Linked LAS1L Gene
title_full_unstemmed Severe Infantile Axonal Neuropathy with Respiratory Failure Caused by Novel Mutation in X-Linked LAS1L Gene
title_short Severe Infantile Axonal Neuropathy with Respiratory Failure Caused by Novel Mutation in X-Linked LAS1L Gene
title_sort severe infantile axonal neuropathy with respiratory failure caused by novel mutation in x-linked las1l gene
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9142081/
https://www.ncbi.nlm.nih.gov/pubmed/35627110
http://dx.doi.org/10.3390/genes13050725
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