Identification of a New Mutation in <i>RSK2</i>, 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 (<i>...
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MDPI AG
2021-08-01
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| Online Access: | https://www.mdpi.com/2076-3425/11/8/1105 |
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| author | Mariateresa Di Stazio Stefania Bigoni Nicola Iuso Josef Vuch Rita Selvatici Sheila Ulivi Pio Adamo d’Adamo |
| author_facet | Mariateresa Di Stazio Stefania Bigoni Nicola Iuso Josef Vuch Rita Selvatici Sheila Ulivi Pio Adamo d’Adamo |
| author_sort | Mariateresa Di Stazio |
| collection | DOAJ |
| 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 (<i>RSK2</i>) 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 <i>RSK2</i> mutation with loss in kinase activity in a three-generation family with an X-linked ID. |
| first_indexed | 2024-03-10T08:57:10Z |
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| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-10T08:57:10Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
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| series | Brain Sciences |
| spelling | doaj.art-1ab9071628f445a29991fbb01a1d76172023-11-22T07:00:11ZengMDPI AGBrain Sciences2076-34252021-08-01118110510.3390/brainsci11081105Identification of a New Mutation in <i>RSK2</i>, the Gene for Coffin–Lowry Syndrome (CLS), in Two Related Patients with Mild and Atypical PhenotypesMariateresa Di Stazio0Stefania Bigoni1Nicola Iuso2Josef Vuch3Rita Selvatici4Sheila Ulivi5Pio Adamo d’Adamo6Institute for Maternal and Child Health-IRCCS “Burlo Garofolo”, 34127 Trieste, ItalyMedical Genetic Unit, Department of Mother and Child, Ferrara University Hospital, 44121 Ferrara, ItalyInstitute for Maternal and Child Health-IRCCS “Burlo Garofolo”, 34127 Trieste, ItalyInstitute for Maternal and Child Health-IRCCS “Burlo Garofolo”, 34127 Trieste, ItalyMedical Genetics Unit, Department of Medical Sciences, University of Ferrara, 44121 Ferrara, ItalyInstitute for Maternal and Child Health-IRCCS “Burlo Garofolo”, 34127 Trieste, ItalyInstitute for Maternal and Child Health-IRCCS “Burlo Garofolo”, 34127 Trieste, ItalyBackground: 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 (<i>RSK2</i>) 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 <i>RSK2</i> mutation with loss in kinase activity in a three-generation family with an X-linked ID.https://www.mdpi.com/2076-3425/11/8/1105<i>RSK2</i> geneCoffin–Lowry syndromeintellectual disabilitykinase assayfunctional assay |
| spellingShingle | Mariateresa Di Stazio Stefania Bigoni Nicola Iuso Josef Vuch Rita Selvatici Sheila Ulivi Pio Adamo d’Adamo Identification of a New Mutation in <i>RSK2</i>, the Gene for Coffin–Lowry Syndrome (CLS), in Two Related Patients with Mild and Atypical Phenotypes Brain Sciences <i>RSK2</i> gene Coffin–Lowry syndrome intellectual disability kinase assay functional assay |
| title | Identification of a New Mutation in <i>RSK2</i>, the Gene for Coffin–Lowry Syndrome (CLS), in Two Related Patients with Mild and Atypical Phenotypes |
| title_full | Identification of a New Mutation in <i>RSK2</i>, the Gene for Coffin–Lowry Syndrome (CLS), in Two Related Patients with Mild and Atypical Phenotypes |
| title_fullStr | Identification of a New Mutation in <i>RSK2</i>, 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 <i>RSK2</i>, the Gene for Coffin–Lowry Syndrome (CLS), in Two Related Patients with Mild and Atypical Phenotypes |
| title_short | Identification of a New Mutation in <i>RSK2</i>, the Gene for Coffin–Lowry Syndrome (CLS), in Two Related Patients with Mild and Atypical Phenotypes |
| title_sort | identification of a new mutation in i rsk2 i the gene for coffin lowry syndrome cls in two related patients with mild and atypical phenotypes |
| topic | <i>RSK2</i> gene Coffin–Lowry syndrome intellectual disability kinase assay functional assay |
| url | https://www.mdpi.com/2076-3425/11/8/1105 |
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