Aims: Primary pulmonary vein stenosis (PVS) is a rare cardiac abnormality that exhibits a high morbidity and mortality rate. The disease is characterized by obstruction of the pulmonary venous blood flow owing to congenital hypoplasia of individual extra-pulmonary veins. We describe a consanguineous Turkish family with four affected siblings with primary PVS in association with prenatal lymphatic abnormalities. We aimed to map the first gene for primary PVS.
Methods and results: Patients had extensive cardiological examinations including electrocardiograms, echocardiograms, ventilation-perfusion scans, and cardiac catheterizations. All patients died before the age of 16 months because of severe progressive primary PVS. Chromosomal analysis revealed normal karyotypes. We performed a genome-wide linkage analysis using 250 K single nucleotide polymorphism arrays and found the first locus for primary PVS on chromosome 2q35-2q36.1 [multipoint logarithms (base 10) of odds (LOD) scores 3.6]. By fine-mapping with microsatellite markers, we confirmed the homozygous region that extended 6.6 Mb (D2S164-D2S133). Sequencing 12 (188 exons) of the 88 genes from the region revealed no disease-causing sequence variations.
Conclusion: Our findings open perspectives for the identification of the genetic cause(s) leading to PVS, which might contribute to elucidate the pathological mechanisms involved in this disorder.