Whole Exome Sequencing for a Patient with Rubinstein-Taybi Syndrome Reveals de Novo Variants besides an Overt CREBBP Mutation

International Journal of Molecular Sciences

Hee Jeong Yoo⁵  Kyung Kim¹  In Hyang Kim⁵  Seong-Hwan Rho³  Jong-Eun Park⁵  Ki Young Lee²  Soon Ae Kim⁶  Byung Yoon Choi⁴  Namshin Kim¹ 

[1] Epigenomics Research Center, Genome Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea; E-Mail:;Department of Biomedical Informatics, Ajou University, School of Medicine, Suwon 443-749, Korea; E-Mail:;Simulacre Modeling Group, Seoul 140-897, Korea; E-Mail:;Department of Psychiatry, Seoul National University, College of Medicine, Seoul 110-744, Korea; E-Mail:;Department of Psychiatry, Seoul National University Hospital, Seongnam, Gyeonggi 463-707, Korea; E-Mails:;Department of Pharmacology, Eulji University College of Medicine, Daejeon 301-746, Korea; E-Mail:

关键词: Rubinstein-Taybi syndrome (RSTS);    Autism spectrum disorder (ASD);    de novo variants;    Tenascin C (TNC) gene;    insulin-like growth factor-binding protein;    acid labile subunit (IGFALS) gene;    CREB (cAMP response element binding protein) binding protein (CREBBP) gene;   

DOI  :  10.3390/ijms16035697

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.