First locus for primary pulmonary vein stenosis maps to chromosome 2q

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

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Scopus)


AimsPrimary 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 resultsPatients 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.ConclusionOur 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.

Original languageEnglish
Pages (from-to)2485-2492
Number of pages8
JournalEuropean Heart Journal
Issue number20
Publication statusPublished - 1 Oct 2009


  • Genome wide
  • Linkage analysis
  • Primary pulmonary vein stenosis
  • SNP arrays


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