Mutations in DDX3X are a common cause of unexplained intellectual disability with gender-specific effects on Wnt signaling

Original research article by Snijders Blok et al. (2015).

Read the abstract here.

This article considers the effect that changes in the DDX3X gene have on females’ behavioral, developmental, and physical features. Participants were females with unexplained intellectual disability (ID). ID affects 1% to 3% of the human population and is more commonly reported in males than in females. The majority of genetic changes associated with ID occur in males. However, changes in the DDX3X gene are more commonly associated with ID in females. This study identified 38 females with de novo (new) DDX3X changes and analyzed their characteristics. The following table lists the common characteristics the researchers observed:

Clinical Features of Females with a DDX3X Gene Change
Percentage (%) Number of individuals with condition
Intellectual disability or developmental delay 100 38/38
Mild or mild-moderate disability 26 10/38
Moderate or moderate-severe disability 26 10/38
Severe disability 40 15/38
Developmental delay 8 3/38
Low weight 32 12/38
Microcephaly 32 12/38
Hypotonia 76 29/38
Epilepsy 16 6/38
Movement disorder (including spasticity) 45 17/38
Behavior problems 53 20/38
Brain MRI
Corpus callosum hypoplasia 35 13/37
Cortical malformation 11 4/37
Ventricular enlargement 35 13/37
Skin abnormalities 37 14/38
Hyperlaxity 37 14/38
Visual problems 34 13/38
Hearing loss 8 3/38
Cleft lip or palate 8 3/38
Precocious puberty 13 5/38
Scoliosis 11 4/38