Journal Article

Further refinement of the differentially methylated distant lung-specific FOXF1 enhancer in a neonate with alveolar capillary dysplasia

Garimella, Rijutha P., Szafranski, Przemyslaw, Silk, Alan, Benheim, Alan, Deutsch, Gail, Hartman, Ryan, Stankiewicz, Paweł, Mani, Haresh

2023

Overview

Heterozygous SNVs or CNV deletions involving the FOXF1 gene, or its distant enhancer, are causative for 80–90% of cases of alveolar capillary dysplasia with misalignment of pulmonary veins. Recently, we proposed bimodal structure and parental functional dimorphism of the lung-specific FOXF1 enhancer, with Unit 1 having higher activity on the paternal chr16 and Unit 2 on the maternal chr16. Here, we describe a novel unusually sized pathogenic de novo copy-number variant deletion involving a portion of the FOXF1 enhancer on maternal chr16 that implies narrowing Unit 2 to an essential ~ 9-kb segment. Using a restrictase-based assay, we found that this enhancer segment is weakly methylated at ApT adenine, with about twice the frequency of methylation on the maternal versus paternal chr16. Our data provide further insight into the FOXF1 enhancer structure and function.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: ACDMPV / Alveoli / Autopsies / Biomedical and Life Sciences / Biomedicine / Developmental lung disorders / Differential methylation / Dimorphism / DNA Methylation / Dysplasia / Enhancer Elements, Genetic / Forkhead Transcription Factors - genetics / Foxf1 gene / Gene Function / Gene regulation / Genes / Genetic testing / Genomes / Human Genetics / Humans / Infant, Newborn / Infants (Newborn) / Intensive care / Lung - pathology / Lungs / Methylation / Neonatology / Persistent Fetal Circulation Syndrome - genetics / Pulmonary arteries / Sequence Deletion / Structure-function relationships / Tissue-specific enhancer