Dataset Information

Clinical exome sequencing identifies novel CREBBP variants in 18 Chinese Rubinstein-Taybi Syndrome kids with high frequency of polydactyly.

ABSTRACT: BACKGROUND:Rubinstein-Taybi syndrome (RSTS) is a rare genetic disease characterized by broad thumbs and halluces, facial dysmorphisms, short stature, and intellectual disability. RSTS is mainly caused by de novo variants in epigenetics-associated gene, CREBBP. To date, there is no cohort study of CREBBP variants in Chinese RSTS patients. METHODS:In this study, 18 kids who meet the main criteria of RSTS were recruited. Molecular diagnoses were analyzed by clinical exome sequencing (CES), and the medical records were reviewed retrospectively. RESULTS:Nineteen novel CREBBP variants in 18 RSTS patients were identified, including two missense, four nonsense, five frameshift, one splicing variants, and seven intragenic deletions. A higher incidence (37%, 7/19) of intragenic deletions was detected. One patient who had two de novo missense variants c.[4112T > A, 4118C > A] in cis and one patient who had a de novo frameshift variant c.5837delC in homozygous state (90%) were found in this study. Compared with the previously reported populations, seven clinical features were different, including the higher incidence of polydactyly, syndactyly, microcephaly, and micrognathia, and the lower incidence of angulated thumbs, autistic behavior, and epilepsy. One patient with obesity in the first year was diagnosed with CREBBP gene exon 2 deletion, was initially suspected of Prader-Willi syndrome. CONCLUSION:We reported the genetic and clinical information of 18 RSTS patients from Chinese population with novel CREBBP variants. This study provides a new insight into RSTS and illustrates the value of applying CES which increases the diagnostic yields and enhances the clinical care of RSTS patients.

SUBMITTER: Yu S

PROVIDER: S-EPMC6900364 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clinical exome sequencing identifies novel CREBBP variants in 18 Chinese Rubinstein-Taybi Syndrome kids with high frequency of polydactyly.

Yu Sha S Wu Bingbing B Qian Yanyan Y Zhang Ping P Lu Yulan Y Dong Xinran X Wang Qing Q Zhao Xuemei X Liu Renchao R Zhou Wenhao W Wang Huijun H

Molecular genetics & genomic medicine 20191022 12

<h4>Background</h4>Rubinstein-Taybi syndrome (RSTS) is a rare genetic disease characterized by broad thumbs and halluces, facial dysmorphisms, short stature, and intellectual disability. RSTS is mainly caused by de novo variants in epigenetics-associated gene, CREBBP. To date, there is no cohort study of CREBBP variants in Chinese RSTS patients.<h4>Methods</h4>In this study, 18 kids who meet the main criteria of RSTS were recruited. Molecular diagnoses were analyzed by clinical exome sequencing ...[more]

PMID: 31637876

Similar Datasets

Project description:Rubinstein-Taybi syndrome (RSTS) is a rare genetic disorder in humans characterized by growth and psychomotor delay, abnormal gross anatomy, and mild to severe mental retardation (Rubinstein and Taybi, Am J Dis Child 105:588-608, 1963, Hennekam et al., Am J Med Genet Suppl 6:56-64, 1990). RSTS is caused by de novo mutations in epigenetics-associated genes, including the cAMP response element-binding protein (CREBBP), the gene-encoding protein referred to as CBP, and the EP300 gene, which encodes the p300 protein, a CBP homologue. Recent studies of the epigenetic mechanisms underlying cognitive functions in mice provide direct evidence for the involvement of nuclear factors (e.g., CBP) in the control of higher cognitive functions. In fact, a role for CBP in higher cognitive function is suggested by the finding that RSTS is caused by heterozygous mutations at the CBP locus (Petrij et al., Nature 376:348-351, 1995). CBP was demonstrated to possess an intrinsic histone acetyltransferase activity (Ogryzko et al., Cell 87:953-959, 1996) that is required for CREB-mediated gene expression (Korzus et al., Science 279:703-707, 1998). The intrinsic protein acetyltransferase activity in CBP might directly destabilize promoter-bound nucleosomes, facilitating the activation of transcription. Due to the complexity of developmental abnormalities and the possible genetic compensation associated with this congenital disorder, however, it is difficult to establish a direct role for CBP in cognitive function in the adult brain. Although aspects of the clinical presentation in RSTS cases have been extensively studied, a spectrum of symptoms found in RSTS patients can be accessed only after birth, and, thus, prenatal genetic tests for this extremely rare genetic disorder are seldom considered. Even though there has been intensive research on the genetic and epigenetic function of the CREBBP gene in rodents, the etiology of this devastating congenital human disorder is largely unknown.

Dataset Information

Clinical exome sequencing identifies novel CREBBP variants in 18 Chinese Rubinstein-Taybi Syndrome kids with high frequency of polydactyly.

Publications

Clinical exome sequencing identifies novel CREBBP variants in 18 Chinese Rubinstein-Taybi Syndrome kids with high frequency of polydactyly.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets