Do paternal deletions involving the FOXF1 locus on chromosome 16q24.1 manifest with more severe non-lung anomalies?

Eur J Med Genet. 2022 May 6:104519. doi: 10.1016/j.ejmg.2022.104519. Online ahead of print.ABSTRACTAlveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal lung developmental disorder in neonates due to heterozygous loss-of-function of the mesenchymal transcription factor gene, FOXF1. Interestingly, unlike ACDMPV-causing point mutations in FOXF1 that can be inherited from the mother or father, causative copy-number variant (CNV) deletions arise de novo and almost exclusively on chromosome 16 inherited from the mother (n = 50 vs. n = 3). Here, we describe a fourth case of a de novo paternal CNV deletion encompassing FOXF1, its neighboring long non-coding RNA gene FENDRR, and their distant lung-specific enhancer, identified in a 21-week-old fetus with tetralogy of Fallot, gastrointestinal and genitourinary abnormalities, a single umbilical artery, and patchy histopathological findings of ACDMPV in lung autopsy. We also review the ACDMPV-causative CNV deletions detected prenatally and propose that the majority of paternal deletions manifest with more severe additional non-lung abnormalities.PMID:35533956 | DOI:10.1016/j.ejmg.2022.104519

Source: European Journal of Medical Genetics - May 9, 2022 Category: Genetics & Stem Cells Authors: Esra Y ıldız Bölükbaşı Justyna A Karolak Tomasz Gambin Przemyslaw Szafranski Gail H Deutsch Pawe ł Stankiewicz Source Type: research