Abstract:

Objective To summarize the clinical and genetic characteristics of X-linked intellectual disability (XLID) caused by DDX3X gene variation. Methods The clinical data of 3 children with XLID caused by DDX3X gene variation who were treated in the rehabilitation department from January 2018 to April 2021 were retrospectively analyzed. Results Case 1 was a boy aged 8 months and 23 days, case 2 was a girl aged 6 months, and case 3 was a girl aged 1 year and 6 months. All the three patients presented with total growth retardation, special facial features and muscle dystonia at the first visit. The whole exome sequencing showed that case 1 had a splicing mutation of C. 1025+3A>C (p?) in the DDX3X gene. The site was heterozygous in the mother and wild-type in the father. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, this variant was of unknown clinical significance. After RT-PCR and Sanger verification, it was found that this mutation could cause partial retention of intron 10 and partial skipping of exon 10, suggesting that the mutation might be a candidate site for abnormal gene function, and this site has not been reported. Patient 2 had a deletion mutation of c.1535-1536delAT (p.H512Rfs*5), which was wild-type in both of her parents. According to ACMG guidelines, this mutation was a de novo pathogenic mutation. In child 3, a splicing mutation of c.679+2T>G was found in the intron 7 region of DDX3X gene. Both of her parents had wild type at this site, and this mutation was a de novo pathogenic mutation. Conclusions In this study, three new DDX3X gene mutation sites were reported for the first time in China and one of them was verified as a candidate site for splicing mutation. Above findings have enriched the mutation spectrum of DDX3X gene and provided a basis for clinical diagnosis and genetic counseling.

Key words: DDX3X gene, X-linked intellectual disability, genetic analysis