Investigation of the MYH11 gene in sporadic patients with an isolated persistently patent arterial duct.

Persistent patency of the arterial duct is one of the most common congenital cardiac malformations. We recently showed that mutations in the MYH11 gene result in a disease combining familial thoracic aortic aneurysm and dissection, along with patency of the arterial duct. It is also known that the smooth muscle myosin heavy chain is involved in the physiological closure of the arterial duct. With this in mind, we investigated whether the MYH11 gene was a susceptibility gene for sporadic occurrence of isolated persistent patency of the arterial duct. We sequenced the entire coding sequence of the MYH11 gene in 60 Caucasian children with persistent patency born after 36 weeks of gestation. The frequencies of rare genetic variants, and single nucleotide polymorphisms, were compared with 192 normal controls. Two possible functional missense mutations were found in two affected individuals. Another rare variant, specifically p.Arg1535Gln, and two coding polymorphisms, namely p.Ala1234Thr and p.Val1289Ala, had allele frequencies similar to those in controls. Haplotype analysis after estimating linkage disequilibrium was carried out using six polymorphisms. Individual genotypes were distributed similarly among cases and controls. Only one of the seven major haplotypes was significantly less frequent among cases, at 0.07, than among controls, when the figure was 0.22 (OR 0.23 [0.08-0.27]). Our findings suggest that the MYH11 gene is involved in only rare instances when persistent patency of the arterial duct occurs in sporadic fashion.