A recurrent 8 bp frameshifting indel in FOXF1 defines a novel mutation hotspot associated with alveolar capillary dysplasia with misalignment of pulmonary veins. Issue 11 (22nd August 2019)

• Record Type: Journal Article
• Authors: Karolak, Justyna A.; Bacolla, Albino; Liu, Qian; Lantz, Patrick E.; Petty, John; Trapane, Pamela; Panzer, Karin; Totapally, Balagangadhar R.; Niu, Zhiyv; Xiao, Rui; Xie, Nina G.; Wu, Lucia R.; Szafranski, Przemyslaw; Zhang, David Y.; Stankiewicz, Paweł
• Is Part Of: American journal of medical genetics. Volume 179:Issue 11(2019)
• Page Start: 2272
• Page End: 2276
• Publication Date: 2019-08-22
• Subjects: CpG island -- FOXF1 haploinsufficiency -- recurrent mutation -- tandem repeats; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.61338
• Languages: English
• ISSNs: 1552-4825

Abstract

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.