ORPHA: 466729;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 6p12.3 | Patent ductus arteriosus 2 | 617035 | Autosomal dominant | 3 | TFAP2B | 601601 |
A number sign (#) is used with this entry because of evidence that patent ductus arteriosus-2 (PDA2) is caused by heterozygous mutation in the TFAP2B gene (601601) on chromosome 6p12.
Mutation in TFAP2B also causes Char syndrome (CHAR; 169100), in which affected individuals exhibit facial dysmorphism and hand abnormalities in addition to patent ductus arteriosus (PDA).
The ductus arteriosus is a muscular artery connecting the pulmonary artery and the aorta during fetal life, shunting blood away from the lungs. It normally occludes shortly after birth. Failure of ductal closure results in PDA, one of the most common congenital heart defects, affecting 1 in 2,000 to 1 in 5,000 full-term infants and constituting 5% to 7% of all congenital heart defects (summary by Mani et al., 2005). PDA can be an isolated anomaly or occur in association with other congenital anomalies (summary by Khetyar et al., 2008).
For a discussion of genetic heterogeneity of isolated PDA, see PDA1 (607411).
Khetyar et al. (2008) studied a consanguineous Kuwaiti family segregating autosomal dominant PDA, with 6 affected family members over 2 generations. Clinical history and physical examination confirmed that no affected individuals exhibited the characteristic craniofacial or fifth finger anomalies of Char syndrome.
Chen et al. (2011) reported 2 Chinese families segregating autosomal dominant isolated PDA. The first family consisted of 2 affected sisters with 3 affected offspring, and the second involved an affected mother and daughter. None of the patients exhibited features of Char syndrome.
In 6 affected members of a consanguineous Kuwaiti family segregating autosomal dominant PDA, Khetyar et al. (2008) sequenced the TFAP2B gene and identified heterozygosity for a splice site mutation (601601.0008) that was not found in 6 unaffected family members.
In 5 affected members of a Chinese family with isolated PDA, Chen et al. (2011) identified heterozygosity for a splice site mutation (601601.0007) in the TFAP2B gene. The authors noted that the same splice site mutation had previously been reported in a large family with Char syndrome (Mani et al., 2005), and stated that the reasons for differences in expression patterns remained unclear. In a mother and daughter from an unrelated Chinese family, Chen et al. (2011) identified heterozygosity for a 4-bp deletion in TFAP2B (601601.0009). Both mutations segregated fully with disease in the respective families, and neither was found in 100 ethnically matched controls. Chen et al. (2011) also analyzed the TFAP2B gene in 100 unrelated Chinese children with isolated PDA and 100 healthy unrelated Chinese children (controls) and identified a novel SNP 34 bp upstream of the TFAP2B transcription initiation site (c.1-34G-A). The A allele was found significantly more frequently among affected individuals than among controls (p = 0.012). The AA genotype was found in 8 affected individuals and in no controls. The authors suggested that this variant should be considered as a potential risk factor for PDA.
Chen, Y.-W., Zhao, W., Zhang, Z.-F., Fu, Q., Shen, J., Zhang, Z., Ji, W., Wang, J., Li, F. Familial nonsyndromic patent ductus arteriosus caused by mutations in TFAP2B. Pediat. Cardiol. 32: 958-965, 2011. [PubMed: 21643846] [Full Text: https://doi.org/10.1007/s00246-011-0024-7]
Khetyar, M., Syrris, P., Tinworth, L., Abushaban, L., Carter, N. Novel TFAP2B mutation in nonsyndromic patent ductus arteriosus. Genet. Test. 12: 457-460, 2008. [PubMed: 18752453] [Full Text: https://doi.org/10.1089/gte.2008.0015]
Mani, A., Radhakrishnan, J., Farhi, A., Carew, K. S., Warnes, C. A., Nelson-Williams, C., Day, R. W., Pober, B., State, M. W., Lifton, R. P. Syndromic patent ductus arteriosus : evidence for haploinsufficient TFAP2B mutations and identification of a linked sleep disorder. Proc. Nat. Acad. Sci. 102: 2975-2979, 2005. [PubMed: 15684060] [Full Text: https://doi.org/10.1073/pnas.0409852102]