Language
English
Publication Date
5-5-2026
Journal
Genomics
DOI
10.1016/j.ygeno.2026.111259
PMID
42097522
Abstract
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal lung developmental disorder caused by haploinsufficiency of FOXF1. While larger-sized coding and noncoding copy-number variant (CNV) deletions involving the FOXF1 locus are detected in approximately half of histopathologically-diagnosed ACDMPV patients, small CNVs remain diagnostically challenging. Here, we revisited an unsolved case of familial ACDMPV with two affected siblings. Whole genome sequencing (WGS) of 30-year-old archival lung autopsy tissue analyzed using AI powered platform revealed a 151 bp CNV deletion involving a highly GC-rich portion of exon 1 of FOXF1 that was not detected using Sanger sequencing and chromosomal microarray analysis. No evidence of parental somatic mosaicism was found. This case illustrates how small CNVs within GC-rich genomic regions can evade conventional diagnostic methods and demonstrates the advantage of hybridization free WGS with AI-based data analyses for resolving unsolved cases.
Keywords
AI-based WGS analysis, Diagnostic challenges, Single exon deletions
Published Open-Access
yes
Recommended Citation
Chan Joiner, Hiuling; Pande, Shruti A; Szafranski, Przemyslaw; et al., "Small Partial Deletion of a Highly Gc-Rich FOXF1 Exon 1 in Two Deceased Siblings With Alveolar Capillary Dysplasia" (2026). Faculty, Staff and Students Publications. 7174.
https://digitalcommons.library.tmc.edu/baylor_docs/7174