Clinical Research and Practice
Clinical and genetic characteristics of 21 children with Rubinstein-Taybi syndrome
Yang Shenghai, Liu Haoran, Li Jiayi, Zhang Yu, Liu Ziqin, Wang Lin, Chen Xiaoli, Shangguan Shaofang
Published 2024-04-02
Cite as Chin J Pediatr, 2024, 62(4): 351-356. DOI: 10.3760/cma.j.cn112140-20230822-00122
Abstract
ObjectiveTo investigate the phenotypes of Rubinstein-Taybi syndrome (RSTS) caused by variants in the CREBBP or EP300 gene, and the correlation between genotype and phenotype.
MethodsThis case series study was performed on pediatric patients who were referred to the Children′s Hospital of Capital Institute of Pediatrics between January 2013 and July 2022. Both point variant and copy number deletion in CREBBP or EP300 gene were detected by whole exome sequencing, chromosomal microarray analysis, or copy number variation sequencing (CNV-seq). The variant categories were summarized and phenotype numbers were re-visited for RSTS patients. Based on variant types, the patients were divided into different groups (point variant or copy number deletion, EP300 or CREBBP point variant, and loss of function or missense variant). Phenotype counts between different groups were compared using the rank-sum test of two independent samples.
ResultsA total of 21 RSTS patients were recruited, including 12 males and 9 females, with ages ranging from 1 month to 14 years and 2 months. Among them, 67% (14/21) had point variants, and 33% (7/21) had copy number deletions. Out of these, 20 variants (95%) were de novo. Among 20 patients finishing phenotype count during re-visit, 95% (19/20) of the patients exhibited developmental delays before the age of 2 years. Additionally, 80% (16/20) of the patients had distinctive facial features. Considering phenotype count, no statistically significant difference was found between point variant (14 cases) and copy number deletion (6 cases) (5.0 (3.0, 7.0) vs. 5.0 (2.5, 5.3), Z=0.75, P=0.452), CREBBP (10 cases) and EP300 gene (4 cases) point variant (5.0 (3.8, 7.0) vs. 4.0 (2.0, 6.0), Z=1.14, P=0.253), and loss of function (9 cases) and missense (5 cases) variant (6.0 (4.5, 7.0) vs. 3.0 (2.5, 5.5), Z=1.54, P=0.121).
ConclusionsPatients with RSTS primarily exhibit developmental delays in early childhood. Specific facial features serve as suggested signs of genetic testing. However, no significant genotype-phenotype correlation is found.
Key words:
CREB-binding protein; E1A-associated p300 protein; Rubinstein-Taybi syndrome
Contributor Information
Yang Shenghai
Department of Neurology, Children′ s Hospital of Capital Institute of Pediatrics, Beijing 100020, China
Liu Haoran
Department of Genetics, Capital Institute of Pediatrics, Beijing 100020, China
Li Jiayi
Department of Genetics, Capital Institute of Pediatrics, Beijing 100020, China
Zhang Yu
Department of Laboratory Center, Capital Institute of Pediatrics, Beijing 100020, China
Liu Ziqin
Department of Endocrinology, Children′s Hospital of Capital Institute of Pediatrics, Beijing 100020, China
Wang Lin
Department of Child Health Care, Children′s Hospital of Capital Institute of Pediatrics, Beijing 100020, China
Chen Xiaoli
Department of Genetics, Capital Institute of Pediatrics, Beijing 100020, China
Shangguan Shaofang
Department of Genetics, Capital Institute of Pediatrics, Beijing 100020, China
