A recurrent 8 bp frameshifting indel in FOXF1 defines a novel mutation hotspot associated with alveolar capillary dysplasia with misalignment of pulmonary veins.

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.

• Authors: Justyna A Karolak, Albino Bacolla, Qian Liu, Patrick E Lantz, John Petty, Pamela Trapane, Karin Panzer, Balagangadhar R Totapally, Zhiyv Niu, Rui Xiao, Nina G Xie, Lucia R Wu, Przemyslaw Szafranski, David Y Zhang, Paweł Stankiewicz
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 179 Issue 11 Pg. 2272-2276 (11 2019) ISSN: 1552-4833 [Electronic] United States
• PMID: 31436901 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• FOXF1 protein, human
• Forkhead Transcription Factors

Topics

• Comparative Genomic Hybridization
• CpG Islands (genetics)
• Enhancer Elements, Genetic
• Female
• Forkhead Transcription Factors (genetics)
• Frameshift Mutation (genetics)
• Haploinsufficiency (genetics)
• Heterozygote
• Humans
• INDEL Mutation (genetics)
• Infant
• Infant, Newborn
• Male
• Persistent Fetal Circulation Syndrome (diagnostic imaging, genetics, pathology)
• Pulmonary Alveoli (abnormalities, diagnostic imaging, pathology)
• Pulmonary Veins (diagnostic imaging, pathology)
• Sequence Deletion
• Tandem Repeat Sequences (genetics)