Abstract
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal lung developmental disease. Affected infants manifest with severe respiratory distress and refractory pulmonary hypertension and uniformly die in the first month of life. Heterozygous point mutations or copy-number variant deletions involving FOXF1 and/or its upstream lung-specific enhancer on 16q24.1 have been identified in the vast majority of ACDMPV patients. We have previously described two unrelated families with a de novo pathogenic frameshift variant c.691_698del (p.Ala231Argfs*61) in the exon 1 of FOXF1. Here, we present a third unrelated ACDMPV family with the same de novo variant and propose that a direct tandem repeat of eight consecutive nucleotides GCGGCGGC within the ~4 kb CpG island in FOXF1 exon 1 is a novel mutation hotspot causative for ACDMPV.
Original language | English (US) |
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Pages (from-to) | 2272-2276 |
Number of pages | 5 |
Journal | American Journal of Medical Genetics, Part A |
Volume | 179 |
Issue number | 11 |
DOIs | |
State | Published - Nov 1 2019 |
Keywords
- CpG island
- FOXF1 haploinsufficiency
- recurrent mutation
- tandem repeats
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)