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 YooNamshin Kim

Abstract

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 ...Continue Reading

References

Jun 1, 1989·Journal of Autism and Developmental Disorders·C LordE Schopler
Mar 13, 1995·American Journal of Medical Genetics·R W Miller, J H Rubinstein
Oct 24, 1998·Journal of Intellectual Disability Research : JIDR·A S Levitas, C S Reid
Dec 10, 1999·Journal of Autism and Developmental Disorders·U RosenhallC Gillberg
Feb 22, 2002·American Journal of Medical Genetics·Jessica A HellingsRamil R Baratang
Jun 19, 2002·Journal of Medical Genetics·I CoupryB Arveiler
Feb 5, 2003·Human Molecular Genetics·Eric KalkhovenDorien J M Peters
May 16, 2003·American Journal of Medical Genetics. Part a·Susan WileyCathy A Stevens
Aug 22, 2003·Proceedings of the National Academy of Sciences of the United States of America·Rusiko BourtchouladzeTim Tully
Jun 1, 1963·American Journal of Diseases of Children·J H RUBINSTEIN, H TAYBI
Aug 18, 2004·Biochemical Pharmacology·Eric Kalkhoven
Feb 12, 2005·American Journal of Human Genetics·Jeroen H RoelfsemaDorien J M Peters
Jun 21, 2006·Cellular and Molecular Life Sciences : CMLS·T M Hallam, R Bourtchouladze
Jul 27, 2006·European Journal of Human Genetics : EJHG·Raoul C M Hennekam
Oct 21, 2006·BMC Medical Genetics·Angela BentivegnaLidia Larizza
Aug 30, 2007·The Journal of Clinical Endocrinology and Metabolism·Horacio M DomenéHéctor G Jasper
Apr 24, 2008·Anesthesiology·Frances ChungColin M Shapiro
Sep 17, 2008·American Journal of Medical Genetics. Part a·E K SchorryG A Grabowski
Apr 8, 2009·Journal of Autism and Developmental Disorders·Cédric GaléraManuel-Pierre Bouvard
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
May 26, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Hayden-William CourtlandShoshana Yakar
Aug 19, 2010·European Journal of Human Genetics : EJHG·Anne Chun-Hui TsaiSau Wai Cheung
Jun 29, 2012·Frontiers in Pharmacology·Stefan WieseAndreas Faissner
Oct 18, 2013·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Shun-Chiao ChangSusan L Santangelo
Nov 21, 2014·Progress in Molecular Biology and Translational Science·Jose P Lopez-AtalayaAngel Barco
Dec 11, 2014·Journal of Autism and Developmental Disorders·Jane WaiteChris Oliver

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Citations

Jan 5, 2017·Cold Spring Harbor Molecular Case Studies·Diane B ZastrowMatthew T Wheeler
Jan 24, 2018·American Journal of Medical Genetics. Part a·Max V BootDaphne de Jong
Aug 25, 2021·Molecular Genetics & Genomic Medicine·Naye ChoiJung Min Ko

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Methods Mentioned

BETA
exome sequencing
X-ray

Software Mentioned

Genome Analysis Toolkit ( GATK )
GATK
IGV
Integrative Genomics Viewer ( IGV ) browser
SAMtools
UCSC genome browser
Burrows Aligner ( BWA )

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