Jiang Yunshu, Li Rong, Li Xiaonan
Department of Children's Health, Nanjing Children's Hospital, Nanjing, Jiangsu 210008, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2024 Aug 10;41(8):966-972. doi: 10.3760/cma.j.cn511374-20230614-00362.
To explore the clinical phenotype and genetic basis of a child with Bainbridge-Ropers syndrome (BRPS).
A child with BRPS who had visited Nanjing Children's Hospital on June 26, 2019 was selected as the study subject. Clinical data of the child was reviewed. Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis.
The child was a 6-month-old girl with peculiar facial features, feeding difficulties, malnutrition, global developmental delay, hypotonia, mildly elevated aminotransferase and ulnar deviation. Results of WES showed that she has harbored a c.1533_1534del variant of the ASXL3 gene. Sanger sequencing confirmed that neither of her parents has carried the same variant. No similar case had been retrieved from the HGMD and ClinVar databases. No frequency for this variant among Asian populations was available in the ExAC, 1000 Genomes, and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1533_1534del variant of the ASXL3 gene was determined to be likely pathogenic (PVS1+PS2+PM2_Supporting).
The ASXL3 gene c.1533_1534del variant probably underlay the BRPS in this child. Above finding has provided a reference for the clinical diagnosis and genetic counseling for children with similar disorders.
探讨1例患有班布里奇-罗佩斯综合征（BRPS）患儿的临床表型及遗传基础。
选取2019年6月26日至南京儿童医院就诊的1例BRPS患儿作为研究对象，回顾其临床资料。提取患儿及其父母外周血样本中的基因组DNA，进行全外显子测序（WES），并通过Sanger测序和生物信息学分析对候选变异进行验证。
该患儿为6月龄女童，有特殊面容、喂养困难、营养不良、全面发育迟缓、肌张力低下、转氨酶轻度升高及尺骨偏斜。WES结果显示，她携带ASXL3基因c.1533_1534del变异。Sanger测序证实其父母均未携带相同变异。HGMD和ClinVar数据库中未检索到类似病例。ExAC、千人基因组和gnomAD数据库中均无该变异在亚洲人群中的频率信息。根据美国医学遗传学与基因组学学会（ACMG）的指南，ASXL3基因c.1533_1534del变异被判定为可能致病（PVS1+PS2+PM2_Supporting）。
ASXL3基因c.1533_1534del变异可能是该患儿患BRPS的病因。上述发现为类似疾病患儿的临床诊断和遗传咨询提供了参考。
