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Identification of a New Mutation in RSK2, the Gene for Coffin–Lowry Syndrome (CLS), in Two Related Patients with Mild and Atypical Phenotypes

Background: Coffin–Lowry syndrome (CLS) is a syndromic form of X-linked intellectual disability, in which specific associated facial, hand, and skeletal abnormalities are diagnostic features. Methods: In the present study, an unreported missense genetic variant of the ribosomal S6 kinase 2 (RSK2) ge...

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Autores principales: Di Stazio, Mariateresa, Bigoni, Stefania, Iuso, Nicola, Vuch, Josef, Selvatici, Rita, Ulivi, Sheila, d’Adamo, Pio Adamo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394959/
https://www.ncbi.nlm.nih.gov/pubmed/34439726
http://dx.doi.org/10.3390/brainsci11081105
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author Di Stazio, Mariateresa
Bigoni, Stefania
Iuso, Nicola
Vuch, Josef
Selvatici, Rita
Ulivi, Sheila
d’Adamo, Pio Adamo
author_facet Di Stazio, Mariateresa
Bigoni, Stefania
Iuso, Nicola
Vuch, Josef
Selvatici, Rita
Ulivi, Sheila
d’Adamo, Pio Adamo
author_sort Di Stazio, Mariateresa
collection PubMed
description Background: Coffin–Lowry syndrome (CLS) is a syndromic form of X-linked intellectual disability, in which specific associated facial, hand, and skeletal abnormalities are diagnostic features. Methods: In the present study, an unreported missense genetic variant of the ribosomal S6 kinase 2 (RSK2) gene has been identified, by next-generation sequencing, in two related males with two different phenotypes of intellectual disability (ID) and peculiar facial dysmorphisms. We performed functional studies on this variant and another one, already reported in the literature, involving the same amino acid residue but, to date, without an efficient characterization. Results: Our study demonstrated that the two variants involving residue 189 significantly impaired its kinase activity. Conclusions: We detected a loss-of-function RSK2 mutation with loss in kinase activity in a three-generation family with an X-linked ID.
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spelling pubmed-83949592021-08-28 Identification of a New Mutation in RSK2, the Gene for Coffin–Lowry Syndrome (CLS), in Two Related Patients with Mild and Atypical Phenotypes Di Stazio, Mariateresa Bigoni, Stefania Iuso, Nicola Vuch, Josef Selvatici, Rita Ulivi, Sheila d’Adamo, Pio Adamo Brain Sci Article Background: Coffin–Lowry syndrome (CLS) is a syndromic form of X-linked intellectual disability, in which specific associated facial, hand, and skeletal abnormalities are diagnostic features. Methods: In the present study, an unreported missense genetic variant of the ribosomal S6 kinase 2 (RSK2) gene has been identified, by next-generation sequencing, in two related males with two different phenotypes of intellectual disability (ID) and peculiar facial dysmorphisms. We performed functional studies on this variant and another one, already reported in the literature, involving the same amino acid residue but, to date, without an efficient characterization. Results: Our study demonstrated that the two variants involving residue 189 significantly impaired its kinase activity. Conclusions: We detected a loss-of-function RSK2 mutation with loss in kinase activity in a three-generation family with an X-linked ID. MDPI 2021-08-22 /pmc/articles/PMC8394959/ /pubmed/34439726 http://dx.doi.org/10.3390/brainsci11081105 Text en © 2021 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
Di Stazio, Mariateresa
Bigoni, Stefania
Iuso, Nicola
Vuch, Josef
Selvatici, Rita
Ulivi, Sheila
d’Adamo, Pio Adamo
Identification of a New Mutation in RSK2, the Gene for Coffin–Lowry Syndrome (CLS), in Two Related Patients with Mild and Atypical Phenotypes
title Identification of a New Mutation in RSK2, the Gene for Coffin–Lowry Syndrome (CLS), in Two Related Patients with Mild and Atypical Phenotypes
title_full Identification of a New Mutation in RSK2, the Gene for Coffin–Lowry Syndrome (CLS), in Two Related Patients with Mild and Atypical Phenotypes
title_fullStr Identification of a New Mutation in RSK2, the Gene for Coffin–Lowry Syndrome (CLS), in Two Related Patients with Mild and Atypical Phenotypes
title_full_unstemmed Identification of a New Mutation in RSK2, the Gene for Coffin–Lowry Syndrome (CLS), in Two Related Patients with Mild and Atypical Phenotypes
title_short Identification of a New Mutation in RSK2, the Gene for Coffin–Lowry Syndrome (CLS), in Two Related Patients with Mild and Atypical Phenotypes
title_sort identification of a new mutation in rsk2, the gene for coffin–lowry syndrome (cls), in two related patients with mild and atypical phenotypes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394959/
https://www.ncbi.nlm.nih.gov/pubmed/34439726
http://dx.doi.org/10.3390/brainsci11081105
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