Bainbridge-Ropers syndrome with ASXL3 gene variation in a child and literature review / 中华儿科杂志

ABSTRACT

Objective@#To investigate the clinical manifestations and genetic features of a child with Bainbridge-Ropers syndrome caused by ASXL3 gene variation and review the literature.@*Methods@#Clinical data and genetic features were collected and analyzed from a child with Bainbridge-Ropers syndrome who was diagnosed in Bao'an Maternity and Child Health Hospital in November 2016. "ASXL3" and "Bainbridge-Ropers" were used as key words to search at China National Knowledge Infrastructure, Wangfang Data Knowledge Service Platform, PubMed and Human Gene Mutation Database up to June 2017.@*Results@#A 29/12 years old girl was presented with psychomotor retardation, feeding difficulty, hypotonia and specific craniofacial phenotype. She showed severe growth retardation (height 84 cm, body weight 8.0 kg (both were less than 3rd percentile rank of the children at the same age) and head circumference 46 cm(=3rd percentile rank)), without obvious abnormalities in laboratory tests and neuroimaging tests. A de novo heterozygous nonsense variation c.3349C>T(p.R1117*) in ASXL3 gene was identified by the whole exome sequencing, and the novel variation was classified into pathologic variant based on Standards and guidelines for the interpretation of sequence variants from ACMG. According to literature retrieval, no Chinese cases with ASXL3 variation had been reported. Totally 28 cases including the present girl harboring ASXL3 variations with detailed clinical information were reported. Thirty-one variations in ASXL3 gene were involved, including 1 missense variation and 30 loss of function variations, which were all de novo variations.@*Conclusions@#The clinical features of Bainbridge-Ropers syndrome include severe psychomotor retardation, feeding difficulties, hypotonia and specific facial features. The heterozygous nonsense variation in ASXL3 gene is the cause of the patient. All the pathogenic variations in ASXL3 gene are de novo and loss of function variations.