Whole exome sequencing for a patient with Rubinstein-Taybi syndrome reveals de Novo variants besides an overt CREBBP mutation

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Whole exome sequencing for a patient with Rubinstein-Taybi syndrome reveals de Novo variants besides an overt CREBBP mutation
H J Yoo; Kyung Kim; I H Kim; S H Rho; J E Park; K Y Lee; S A Kim; B Y Choi; Namshin Kim
Bibliographic Citation
International Journal of Molecular Sciences, vol. 16, no. 3, pp. 5697-5713
Publication Year
Rubinstein-Taybi syndrome (RSTS) is a rare condition with a prevalence of 1 in 125,000-720,000 births and characterized by clinical features that include facial, dental, and limb dysmorphology and growth retardation. Most cases of RSTS occur sporadically and are caused by de novo mutations. Cytogenetic or molecular abnormalities are detected in only 55% of RSTS cases. Previous genetic studies have yielded inconsistent results due to the variety of methods used for genetic analysis. The purpose of this study was to use whole exome sequencing (WES) to evaluate the genetic causes of RSTS in a young girl presenting with an Autism phenotype. We used the Autism diagnostic observation schedule (ADOS) and Autism diagnostic interview revised (ADI-R) to confirm her diagnosis of Autism. In addition, various questionnaires were used to evaluate other psychiatric features. We used WES to analyze the DNA sequences of the patient and her parents and to search for de novo variants. The patient showed all the typical features of Autism, WES revealed a de novo frameshift mutation in CREBBP and de novo sequence variants in TNC and IGFALS genes. Mutations in the CREBBP gene have been extensively reported in RSTS patients, while potential missense mutations in TNC and IGFALS genes have not previously been associated with RSTS. The TNC and IGFALS genes are involved in central nervous system development and growth. It is possible for patients with RSTS to have additional de novo variants that could account for previously unexplained phenotypes.
Acid labile subunit (IGFALS) geneAutism spectrum disorder (ASD)CREB (cAMP response element binding protein) binding protein (CREBBP) geneDe novo variantsInsulin-like growth factor-binding proteinRubinstein-Taybi syndrome (RSTS)Tenascin C (TNC) gene
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Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
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