کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2815431 1159871 2016 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Concomitant partial exon skipping by a unique missense mutation of RPS6KA3 causes Coffin–Lowry syndrome
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی ژنتیک
پیش نمایش صفحه اول مقاله
Concomitant partial exon skipping by a unique missense mutation of RPS6KA3 causes Coffin–Lowry syndrome
چکیده انگلیسی


• A patient with Coffin–Lowry syndrome having a novel RPS6KA3 missense mutation.
• The first exonic mutation causing exon 8 skipping of RPS6KA3.
• A carrier mother with a hemizygous mutation had only wildtype transcripts.
• Mother with moderately skewed X-inactivation consistent with her mild phenotype.
• The mutation in the ATP binding pocket alters protein function.

Coffin–Lowry syndrome (CLS) is an X-linked semi-dominant disorder characterized by diverse phenotypes including intellectual disability, facial and digital anomalies. Loss-of-function mutations in the Ribosomal Protein S6 Kinase Polypeptide 3 (RPS6KA3) gene have been shown to be responsible for CLS. Among the large number of mutations, however, no exonic mutation causing exon skipping has been described. Here, we report a male patient with CLS having a novel mutation at the 3′ end of an exon at a splice donor junction. Interestingly, this nucleotide change causes both a novel missense mutation and partial exon skipping leading to a truncated transcript. These two transcripts were identified by cDNA sequencing of RT-PCR products. In the carrier mother, we found only wildtype transcripts suggesting skewed X-inactivation. Methylation studies confirmed X-inactivation was skewed moderately, but not completely, which is consistent with her mild phenotype. Western blot showed that the mutant RSK2 protein in the patient is expressed at similar levels relative to his mother. Protein modeling demonstrated that the missense mutation is damaging and may alter binding to ATP molecules. This is the first report of exon skipping from an exonic mutation of RPS6KA3, demonstrating that a missense mutation and concomitant disruption of normal splicing contribute to the manifestation of CLS.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gene - Volume 575, Issue 1, 1 January 2016, Pages 42–47
نویسندگان
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