Abstract
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare developmental lung disorder that is uniformly lethal. Affected infants die within the first few weeks of their life despite aggressive treatment, although a few cases of late manifestation and longer survival have been reported. We have shown previously that mutations and deletions in FOXF1 are a cause of this disorder. Although most of the cases of ACD/MPV are sporadic, there have been infrequent reports of familial cases. We present a family with five out of six children affected with ACD/MPV. DNA analysis identified a missense mutation (c.416G>T; p.Arg139Leu) in the FOXF1 gene that segregated in the three affected siblings tested. The same variant is also present as a de novo mutation in the mother and arose on her paternally derived chromosome 16. The two tested affected siblings share the same chromosome 16 haplotype inherited from their maternal grandfather. Their single healthy sibling has a different chromosome 16 haplotype inherited from the maternal grandmother. The results are consistent with paternal imprinting of FOXF1 in human.