CCN1 mutation is associated with atrial septal defect.

Area of Science:

• Genetics
• Cardiology
• Developmental Biology

Background:

• Congenital heart disease (CHD) genetic causes are often unknown.
• CCN1/CYR61, a regulatory factor, is implicated in cardiac development.
• A novel mouse model suggests CCN1's role in heart morphogenesis.

Purpose of the Study:

• Investigate the role of CCN1 in atrial septal defects (ASD).
• Identify potential genetic links between CCN1 mutations and ASD in humans.
• Highlight CCN1 as a candidate gene for CHD genetic analysis.

Main Methods:

• Candidate gene sequencing of CCN1 coding exons in 143 ASD patients.
• Bioinformatic analysis of identified mutations.
• Exclusion analysis in over 1,000 controls and public databases.

Main Results:

• Identified a rare heterozygous missense mutation (p.R47W) in CCN1 in one severe ASD patient.
• The mutation affects a conserved N-terminal IGFBP module residue.
• Exclusion in extensive controls and databases supports p.R47W as disease-associated.

Conclusions:

• The CCN1 p.R47W variant is a probable cause of ASD.
• This study is the first to link CCN1 mutations to ASD.
• CCN1 warrants further investigation in congenital heart disease genetics.