Open AccessClinical exome sequencing identifies novel CREBBP variants in 18 Chinese Rubinstein–Taybi Syndrome kids with high frequency of polydactyly
Author(s) -
Yu Sha,
Wu Bingbing,
Qian Yanyan,
Zhang Ping,
Lu Yulan,
Dong Xinran,
Wang Qing,
Zhao Xuemei,
Liu Renchao,
Zhou Wenhao,
Wang Huijun
Publication year - 2019
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1009
Subject(s) - rubinstein–taybi syndrome , exome sequencing , medicine , genetics , frameshift mutation , polydactyly , kabuki syndrome , medical genetics , intellectual disability , missense mutation , genetic counseling , pediatrics , biology , dermatology , exon , mutation , gene
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.