ALVEOLAR CAPILLARY DYSPLASIA WITH MISALIGNMENT OF PULMONARY VEINS (ACD/MPV)

FOXF1 GENE ANALYSIS IN PATIENTS WITH ACD/MPV

Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV) is a lethal condition characterised by a failure of vascularisation of pulmonary alveolae, leading to complete failure of gas exchange within the lungs. The condition may be associated with congenital malformations including congenital heart defects, intestinal atresias, intestinal malrotation, renal malformations, and vertebral malformations.

ACD/MPV is caused by haploinsufficiency of the FOXF1 gene and disease-causing variants in the gene are identified in 70% of patients (Stankiewicz et al. 2009 Am J Hum Genet 84(6):780-91; Sen et al. 2013 Hum Mutat 34: 801-811).  Deletions in an upstream regulatory region, 257kb upstream of the FOXF1 gene, have been reported (Stankiewicz et al. 2009 Am J Hum Genet 84(6):780-91; Szafranski et al. 2013 Genome Res 23: 23-33). 80% of FOXF1 variants identified to date has arisen de novo but a small number of familial cases have also been reported (Sen et al. 2012 EJHG 21: 474-477; Sen et al. 2013 Hum Mutat 34: 801-811). The FOXF1 gene is paternally imprinted through differentially methylated CpG islands in the upstream regulatory region on 16q24.1 (Szafranski et al. 2013 Genome Res 23: 23-33).  Testing of the parents of affected individuals with FOXF1 disease-causing variants is recommended to determine the pattern of inheritance and recurrence risk.

The laboratory participates in the European Molecular Genetics Quality Network (EMQN) sequencing scheme.