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

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. Cytogene...

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Autores principales: Yoo, Hee Jeong, Kim, Kyung, Kim, In Hyang, Rho, Seong-Hwan, Park, Jong-Eun, Lee, Ki Young, Kim, Soon Ae, Choi, Byung Yoon, Kim, Namshin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394500/
https://www.ncbi.nlm.nih.gov/pubmed/25768348
http://dx.doi.org/10.3390/ijms16035697
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author Yoo, Hee Jeong
Kim, Kyung
Kim, In Hyang
Rho, Seong-Hwan
Park, Jong-Eun
Lee, Ki Young
Kim, Soon Ae
Choi, Byung Yoon
Kim, Namshin
author_facet Yoo, Hee Jeong
Kim, Kyung
Kim, In Hyang
Rho, Seong-Hwan
Park, Jong-Eun
Lee, Ki Young
Kim, Soon Ae
Choi, Byung Yoon
Kim, Namshin
author_sort Yoo, Hee Jeong
collection PubMed
description 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.
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spelling pubmed-43945002015-05-21 Whole Exome Sequencing for a Patient with Rubinstein-Taybi Syndrome Reveals de Novo Variants besides an Overt CREBBP Mutation Yoo, Hee Jeong Kim, Kyung Kim, In Hyang Rho, Seong-Hwan Park, Jong-Eun Lee, Ki Young Kim, Soon Ae Choi, Byung Yoon Kim, Namshin Int J Mol Sci Article 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. MDPI 2015-03-11 /pmc/articles/PMC4394500/ /pubmed/25768348 http://dx.doi.org/10.3390/ijms16035697 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yoo, Hee Jeong
Kim, Kyung
Kim, In Hyang
Rho, Seong-Hwan
Park, Jong-Eun
Lee, Ki Young
Kim, Soon Ae
Choi, Byung Yoon
Kim, Namshin
Whole Exome Sequencing for a Patient with Rubinstein-Taybi Syndrome Reveals de Novo Variants besides an Overt CREBBP Mutation
title Whole Exome Sequencing for a Patient with Rubinstein-Taybi Syndrome Reveals de Novo Variants besides an Overt CREBBP Mutation
title_full Whole Exome Sequencing for a Patient with Rubinstein-Taybi Syndrome Reveals de Novo Variants besides an Overt CREBBP Mutation
title_fullStr Whole Exome Sequencing for a Patient with Rubinstein-Taybi Syndrome Reveals de Novo Variants besides an Overt CREBBP Mutation
title_full_unstemmed Whole Exome Sequencing for a Patient with Rubinstein-Taybi Syndrome Reveals de Novo Variants besides an Overt CREBBP Mutation
title_short Whole Exome Sequencing for a Patient with Rubinstein-Taybi Syndrome Reveals de Novo Variants besides an Overt CREBBP Mutation
title_sort whole exome sequencing for a patient with rubinstein-taybi syndrome reveals de novo variants besides an overt crebbp mutation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394500/
https://www.ncbi.nlm.nih.gov/pubmed/25768348
http://dx.doi.org/10.3390/ijms16035697
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