Paternal Low-Level Mosaicism-Caused SATB2-Associated Syndrome

Area of Science:

• Genetics
• Molecular Biology
• Developmental Biology

Background:

• SATB2-associated syndrome (SAS) is an autosomal dominant disorder linked to SATB2 gene mutations.
• Current diagnostic methods struggle with detecting small deletions and low-level mosaicism in SAS.
• Genetic variations in SATB2 at 2q33.1 are crucial for neurodevelopment and craniofacial formation.

Observation:

• A Chinese Han family presented with SAS, characterized by developmental delay and dental abnormalities in two siblings.
• SNP array identified a 4.9-kb deletion in SATB2 in affected siblings, but not in parents.
• Prenatal diagnosis confirmed the deletion in a third child, leading to pregnancy termination.

Findings:

• Gap-PCR revealed the SATB2 deletion was inherited from the father, with mosaicism indicated by a weaker band.
• The deletion spans 3,013 bp, encompassing exon 9 and parts of introns 8 and 9 of the SATB2 gene.
• Droplet digital PCR quantified paternal mosaicism at 13.2% in blood DNA and 16.7% in semen DNA.

Implications:

• This study highlights paternal low-level mosaicism as a cause of SAS due to intragenic SATB2 deletions.
• Effective diagnostic technologies, including gap-PCR and droplet digital PCR, are crucial for identifying such deletions.
• Understanding mosaicism in SAS improves genetic counseling and prenatal diagnosis for affected families.