The Xp contiguous deletion syndrome and autism

Area of Science:

• Genetics
• Developmental Biology
• Human Genetics

Background:

• Xp22 nullisomy in males leads to a recognizable phenotype due to gene loss.
• Females with similar Xp deletions typically exhibit milder or different clinical manifestations.

Observation:

• A 10-year-old female presented with autism, moderate intellectual disability, and dysmorphic features.
• A de novo interstitial deletion of 5.5 Mb in the Xp22.2p22.32 region was identified on the paternal X chromosome, encompassing 18 genes.

Findings:

• The deletion was characterized using FISH, STR, and array comparative genomic hybridization (CGH).
• Unfavorable skewing of X-inactivation of the maternal X chromosome was observed.
• Comparison with previously reported cases suggests variability in phenotypic expression.

Implications:

• The study underscores the significance of X chromosome gene dosage, deletion characteristics (size, parental origin), and X-inactivation patterns in female development.
• These factors collectively influence the pathogenesis and spectrum of neurodevelopmental and physical abnormalities in individuals with Xp22 deletions.