Ingrid van de Laar, Marja Wessels, Ingrid Frohn-Mulder, Michiel Dalinghaus, Bianca de Graaf, Marianne van Tienhoven, Paul van der Moer, Margreet Husen-Ebbinge, Maarten Lequin, Dennis Dooijes, Ronald de Krijger, Ben A. Oostra, Aida M. Bertoli-Avella
Erasmus Medical Center. Medical Center Rijnmond-Zuid.
Netherlands
European Heart Journal
Eur Heart J 2009; 30: 2485–2492
DOI: 10.1093/eurheartj/ehp271
Abstract
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.
Category
Stenosis or Obstruction of Normal Pulmonary Venous Connections
Genetic Factors Influencing the Onset, Severity or Outcome of Disease
Length of Life Associated with Pulmonary Venous Obstruction
Year of Publication: 2009
Age Focus: Pediatric
Article Type: Case Reports or Retrospective Observations in Small Groups of Patients (≤10 patients)
Article Access: Free PDF File or Full Text Article Available Through PubMed or DOI: Yes