ORPHA: 1478; DO: 0110110;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 15q14 | Atrial septal defect 5 | 612794 | Autosomal dominant | 3 | ACTC1 | 102540 |
A number sign (#) is used with this entry because of evidence that atrial septal defect-5 (ASD5) is caused by heterozygous mutation in the ACTC1 gene (102540) on chromosome 15q14.
For a phenotypic description and discussion of genetic heterogeneity in atrial septal defect, see ASD1 (108800).
Matsson et al. (2008) studied 2 large Swedish families segregating autosomal dominant isolated secundum atrial septal defect (ASD) with variable clinical expression. Genotyping with microsatellite markers in 'family 1' revealed a specific haplotype in all affected individuals spanning a 15.1-cM region of chromosome 15q13-q21; analysis of 'family 2' identified a minimal haplotype with significant linkage to ASD consisting of markers GT44248, GATA12322, and ACTC. All affected individuals genotyped had identical allele sizes for the marker haplotype, suggesting a shared ancestral mutation for the 2 families. A 2-point lod score of 4.8 was obtained for marker ACTC, located within intron 4 of the ACTC1 gene.
Matsson et al. (2008) analyzed the ACTC1 gene in 2 large Swedish families segregating autosomal dominant ASD and identified heterozygosity for a mutation (M123V; 102540.0005) in the 20 available affected individuals. The authors studied 408 additional individuals referred for sporadic congenital heart disease and identified a 17-bp deletion in the ACTC1 gene in a 10-year-old girl with secundum ASD (102540.0006); the mutation was also identified in her clinically unaffected 43-year-old father, who was found to have an abnormal echocardiogram with a posteriorly deviated interventricular septum, believed to be associated with a spontaneously closed perimembranous ventricular septal defect, causing aortic valve regurgitation. Neither mutation was found in 580 control samples.
Matsson, H., Eason, J., Bookwalter, C. S., Klar, J., Gustavsson, P., Sunnegardh, J., Enell, H., Jonzon, A., Vikkula, M., Gutierrez, I., Granados-Riveron, J., Pope, M., Bu'Lock, F., Cox, J., Robinson, T. E., Song, F., Brook, D. J., Marston, S., Trybus, K. M., Dahl, N. Alpha-cardiac actin mutations produce atrial septal defects. Hum. Molec. Genet. 17: 256-265, 2008. [PubMed: 17947298] [Full Text: https://doi.org/10.1093/hmg/ddm302]