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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9142081 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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