Published online Dec 26, 2020. doi: 10.12998/wjcc.v8.i24.6465
Peer-review started: August 28, 2020
First decision: September 24, 2020
Revised: October 8, 2020
Accepted: October 26, 2020
Article in press: October 26, 2020
Published online: December 26, 2020
Processing time: 113 Days and 13.5 Hours
Bainbridge-Ropers syndrome (BRPS) is a severe disorder characterized by failure to thrive, facial dysmorphism, and severe developmental delay. BRPS is caused by a heterozygous loss-of-function mutation in the ASXL3 gene. Due to limited knowledge of the disease and lack of specific features, clinical diagnosis of this syndrome is challenging. With the use of trio-based whole exome sequencing, we identified a novel ASXL3 mutation in a Chinese boy with BRPS and performed a literature review.
A 3-year-old Chinese boy was referred to our hospital due to progressive postnatal microcephaly and intellectual disability with severe speech impairment for 2 years. His other remarkable clinical features were shown as follows: Facial dysmorphism, feeding difficulties, poor growth, motor delay, and abnormal behavior. For the proband, regular laboratory tests, blood tandem mass spectrometry, urine gas chromatographic mass spectrometry, karyotype, hearing screening, and brain magnetic resonance imaging were performed, with negative results. Therefore, for the proband and his unaffected parents, trio-based whole exome sequencing and subsequent validation by Sanger sequencing were performed. A novel nonsense variant in exon 11 of the ASXL3 gene (c.1795G>T; p.E599*) was detected, present in the patient but absent from his parents. Taking into account the concordant phenotypic features of our patient with reported BRPS patients and the detected truncated variant located in the known mutational cluster region, we confirmed a diagnosis of BRPS for this proband. The rehabilitation treatment seemed to have a mild effect.
In this case, a novel nonsense mutation (c.1795G>T, p.E599*) in ASXL3 gene was identified in a Chinese boy with BRPS. This finding not only contributed to better genetic counseling and prenatal diagnosis for this family but also expanded the pathogenic mutation spectrum of ASXL3 gene and provided key information for clinical diagnosis of BRPS.
Core Tip: This report introduces a Chinese boy referred to our hospital mainly due to progressive postnatal microcephaly and intellectual disability with severe speech impairment. A novel pathogenic mutation (c.1795G>T; p.E599*) was detected in the patient by trio-based whole exome sequencing. The proband’s clinical features largely conformed to reported Bainbridge-Ropers syndrome patients in the literature. These clinical and genetic findings improved our understanding of Bainbridge-Ropers syndrome and also aided in the definitive diagnosis and genetic counseling for this family.