<i><scp>RSK2</scp></i> mutation co‐segregates with X‐linked intellectual disability and attenuated Coffin–Lowry phenotype in a three‐generation family

Maystadt, Isabelle; Destrée, Anne; Benoît, Valérie; Aeby, Alec; Lederer, Damien; Moortgat, Stéphanie; Jurkiewicz, Dorota; Krajewska‐Walasek, Małgorzata; Hanauer, André; Thomas, George

doi:10.1111/cge.12122

Cited by 2 publications

(3 citation statements)

References 9 publications

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“…A similar situation pertains in other entities caused by defects in different components of the same complex such as Cornelia de Lange syndrome and Bardet–Biedl syndrome. Although pathogenic ARID1B variants have been identified in 0.9% of a large cohort of individuals with nonsyndromic intellectual disability [Hoyer et al., ], this still does not argue against CSS as a genuine entity, as the percentage of mutations is so much higher in CSS patients (44%), and similar situations are now occurring with other genes such as TCF4 and RSK2 [Rauch et al., ; Maystadt et al., ].…”

Section: Discussionmentioning

confidence: 99%

Coffin-Siris Syndrome and the BAF Complex: Genotype-Phenotype Study in 63 Patients

et al. 2013

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De novo germline variants in several components of the SWI/SNF-like BAF complex can cause Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NCBRS), and nonsyndromic intellectual disability. We screened 63 patients with a clinical diagnosis of CSS for these genes (ARID1A, ARID1B, SMARCA2, SMARCA4, SMARCB1, and SMARCE1) and identified pathogenic variants in 45 (71%) patients. We found a high proportion of variants in ARID1B (68%). All four pathogenic variants in ARID1A appeared to be mosaic. By using all variants from the Exome Variant Server as test data, we were able to classify variants in ARID1A, ARID1B, and SMARCB1 reliably as being pathogenic or nonpathogenic. For SMARCA2, SMARCA4, and SMARCE1 several variants in the EVS remained unclassified, underlining the importance of parental testing. We have entered all variant and clinical information in LOVD-powered databases to facilitate further genotype-phenotype correlations, as these will become increasingly important because of the uptake of targeted and untargeted next generation sequencing in diagnostics. The emerging phenotype-genotype correlation is that SMARCB1 patients have the most marked physical phenotype and severe cognitive and growth delay. The variability in phenotype seems most marked in ARID1A and ARID1B patients. Distal limbs anomalies are most marked in ARID1A patients and least in SMARCB1 patients. Numbers are small however, and larger series are needed to confirm this correlation.

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Section: Discussionmentioning

confidence: 99%

Coffin-Siris Syndrome and the BAF Complex: Genotype-Phenotype Study in 63 Patients

et al. 2013

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“…Coffin-Lowry syndrome (CLS) (MIM 303600) is a rare X-linked dominant disorder, first described by Grange S. Coffin in 1966 and characterized by intellectual disability (ID) and peculiar facial dysmorphisms, hands, and skeletal malformations [1].…”

Section: Introductionmentioning

confidence: 99%

“…In male patients with CLS, moderate-to-severe intellectual disability, abnormal gait, skeletal abnormalities and characteristic facial changes are the rule. Moreover, they typically have hypotonia, delayed closure of the anterior fontanel, facial dysmorphisms, short stature, tapering, hyperextensible fingers, and progressive skeletal deformities, whereas carrier females may show a typical CLS phenotype but are commonly mildly affected [1,5].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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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RSK2 mutation co‐segregates with X‐linked intellectual disability and attenuated Coffin–Lowry phenotype in a three‐generation family

Cited by 2 publications

References 9 publications

Coffin-Siris Syndrome and the BAF Complex: Genotype-Phenotype Study in 63 Patients

Coffin-Siris Syndrome and the BAF Complex: Genotype-Phenotype Study in 63 Patients

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

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