Growth Concerns in Coffin–Lowry Syndrome: A Case Report and Literature Review

Lv, Ying; Zhu, Liuyan; Zheng, Jun; Wu, Dingwen; Shao, Jie

doi:10.3389/fped.2018.00430

Cited by 7 publications

(4 citation statements)

References 23 publications

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“…Phosphorylation of substrates by RSK2 is important during development; thus, germline loss-of-function variants in RPS6KA3 , the gene encoding RSK2, cause Coffin-Lowry syndrome, a disorder characterized by growth and developmental delay as well as other skeletal anomalies ( 35 , 36 , 37 , 38 ). The recent identification of SPRED2 loss-of-function variants in individuals with Noonan syndrome, which also has phenotypic skeletal features, suggests a genetic link between SPRED2 and RSK2 with implications for proper skeletal development ( 11 , 39 ).…”

Section: Discussionmentioning

confidence: 99%

The ribosomal S6 kinase 2 (RSK2)–SPRED2 complex regulates the phosphorylation of RSK substrates and MAPK signaling

Lopez

Bonsor

Sale

et al. 2023

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

The ribosomal S6 kinase 2 (RSK2)–SPRED2 complex regulates the phosphorylation of RSK substrates and MAPK signaling

Lopez

Bonsor

Sale

et al. 2023

Journal of Biological Chemistry

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“…With advancing molecular technology, molecular genetic techniques are being used for the diagnosis of genetic diseases, facilitating the early diagnosis and monitoring of patients. From the perspective of CLS cases, diagnosis in recent years has mostly relied on high-throughput sequencing technology [ 13 , 14 , 15 ]. In this study, a high-throughput sequencing platform was used for sequencing.…”

Section: Discussionmentioning

confidence: 99%

Coffin-Lowry Syndrome Induced by RPS6KA3 Gene Variation in China: A Case Report in Twins

Jin

Shu

2022

Medicina

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Background and objectives: Coffin-Lowry Syndrome (CLS), a rare neurodegenerative disorder, is mainly diagnosed based on clinical manifestations and molecular analyses. In total, about 20 cases of CLS have been reported in China. Here, we report two cases of CLS in identical twin brothers and examine their potential causative mutations. Methods: The Trio mode was used in this analysis, i.e., DNA from the proband and his parents was sequenced. Furthermore, DNA from the proband’s twin brother was used for confirmation. Results: A hemizygous variation was detected in the 11th exon of the RPS6KA3 gene, c.898C>T (p.R300*) of the proband, and the same site variation was detected in his identical twin brother; however, the mutation was not detected in his parents. Conclusions: The RPS6KA3 gene mutation c.898C>T (p.R300*) is the causative factor of familial CLS. The variant detected was reported for the first time in the Chinese population. Additionally, by analyzing the previous literature, we were able to summarize the phenotypic and genetic characteristics of GLS in China.

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“…A total of 13–20% of male CLS and 3–7% of female CLS presented with stimulus-induced drop episodes (SIDEs) ( Rojnueangnit et al, 2014 ). In addition, a few CLS patients presented with diabetes type 2 ( Boulos et al, 2021 ), epileptic seizures ( Gschwind et al, 2015 ), growth retardation ( Lv et al, 2019 ), and hearing or vision problems ( Hunter, 2002 ). The risk of childhood-onset schizophrenia (COS) might be increased in CLS patients ( Ambalavanan et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Chinese female patients with a heterozygous pathogenic RPS6KA3 gene variant c.898C>T and distal 22q11.2 microdeletion

Cong

Jin

Wu³

et al. 2022

Front. Genet.

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Background: Coffin–Lowry syndrome (CLS) [OMIM#303600] is a rare X-linked dominant syndrome. CLS is caused by highly heterogeneous loss-of-function mutations in the RPS6KA3 gene (OMIM*300,075). CLS is characterized by intellectual disability (ID), short stature, tapered fingers, characteristic facial features, and progressive skeletal changes. Distal 22q11.2 microdeletion syndrome (OMIM#611867) is an autosomal dominant and recurrent genomic disorder. It mainly includes three types [distal type I (D–E/F), type II (E–F), and type III (F–G)] and exhibits variable clinical phenotypes (mild, moderate, or even normal): preterm birth, pre- and/or postnatal growth restriction, development delay, ID, behavioral problems, cardiovascular defects, skeletal anomalies, and dysmorphic facial features. We investigated the genetic etiology of a Chinese pedigree with ID, short stature, digit abnormalities, facial dysmorphism, and menstrual disorder. A heterozygous RPS6KA3 gene variant c.898C>T (p.R300X) was identified in this familial case. Two female CLS patients with distal 22q11.2 microdeletion presented with more severe clinical phenotypes. We provided clinical characteristics of these Chinese female CLS patients.Case presentation: We described a Chinese family with three affected females (the mother, the elder sister, and the proband). The mother and the elder sister had more severe clinical phenotypes (moderate facial dysmorphism, more severe cognitive impairment, and shorter stature). The common characteristic phenotypes are ID, short stature, facial dysmorphism, irregular menstruation, and cardiovascular disorders. Peripheral blood samples were collected from the pedigree. Whole-exome sequencing (WES) identified a heterozygous nonsense RPS6KA3 gene variant c.898C>T (p.R300X). It was verified by Sanger sequencing. Copy number variation sequencing (CNV-seq) showed that both the mother and the elder sister carried a CNVseq [hg19] del (22) (q11.22-q11.23) (22997582–23637176)×0.5. RNA from peripheral blood samples was used for measuring the relative quantification of mRNA (expressed by exon 14 of RPS6KA3). The levels of mRNA relative expressions were significantly lower in the mother’s and the elder sister’s blood samples. The levels of mRNA relative expressions were significantly higher in the proband’s blood sample. X-chromosome inactivation (XCI) studies demonstrated that the proband showed extremely skewed XCI, and the XCI pattern of the elder sister was random.Conclusion: Herein, we reported three Chinese female patients with a heterozygous nonsense RPS6KA3 gene variant c.898C>T. Further genetic studies were performed. To our knowledge, Chinese patients with this variant have not been previously reported in the literature. The three female patients presented with variable degrees of severity. The clinical characteristics of these Chinese female CLS patients could expand the phenotypic spectrum of CLS. We helped physicians to understand the genotype–phenotype correlation further.

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Growth Concerns in Coffin–Lowry Syndrome: A Case Report and Literature Review

Cited by 7 publications

References 23 publications

The ribosomal S6 kinase 2 (RSK2)–SPRED2 complex regulates the phosphorylation of RSK substrates and MAPK signaling

The ribosomal S6 kinase 2 (RSK2)–SPRED2 complex regulates the phosphorylation of RSK substrates and MAPK signaling

Coffin-Lowry Syndrome Induced by RPS6KA3 Gene Variation in China: A Case Report in Twins

Case Report: Chinese female patients with a heterozygous pathogenic RPS6KA3 gene variant c.898C>T and distal 22q11.2 microdeletion

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