DPF2-related Coffin-Siris syndrome type 7 in two generations

Area of Science:

• Genetics
• Human Disease
• Molecular Biology

Background:

• Coffin-Siris syndrome type 7 is a rare genetic disorder.
• Previously, all reported cases involved de novo DPF2 gene variants with dominant-negative effects.
• The PHD1/PHD2 domains of DPF2 are critical regions for variant localization.

Observation:

• This study presents the first familial case of Coffin-Siris syndrome type 7.
• The index patient exhibited failure to thrive and ectodermal anomalies.
• Genetic analysis revealed a likely pathogenic DPF2 variant in the PHD1 region.

Findings:

• The mother and older brother of the index patient also carried the DPF2 variant heterozygously.
• The mother presented with mild symptoms, including school difficulties.
• The brother showed developmental delay, autistic features, and ectodermal anomalies, but no growth failure.

Implications:

• This is the first report of an inherited likely pathogenic DPF2 variant in Coffin-Siris syndrome type 7.
• The findings underscore the significant phenotypic variability associated with DPF2 variants.
• Considering inherited DPF2 variants is crucial for accurate variant filtering in whole exome sequencing data analysis.