High-level gonosomal mosaicism for a pathogenic non-coding CNV deletion of the lung-specific FOXF1 enhancer in an unaffected mother of an infant with ACDMPV.
Mol Genet Genomic Med
; 10(11): e2062, 2022 11.
Article
in En
| MEDLINE
| ID: mdl-36124617
ABSTRACT
BACKGROUND:
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) results from haploinsufficiency of the mesenchymal transcription factor FOXF1 gene. To date, only one case of an ACDMPV-causative CNV deletion inherited from a very-low level somatic mosaic mother has been reported.METHODS:
Clinical, histopathological, and molecular studies, including whole genome sequencing, chromosomal microarray analysis, qPCR, and Sanger sequencing, followed by in vitro fertilization (IVF) with preimplantation genetic testing (PGT) were used to study a family with a deceased neonate with ACDMPV.RESULTS:
A pathogenic CNV deletion of the lung-specific FOXF1 enhancer in the proband was found to be inherited from an unaffected mother, 36% mosaic for this deletion in her peripheral blood cells. The qPCR analyses of saliva, buccal cells, urine, nail, and hair samples revealed 19%, 18%, 15%, 19%, and 27% variant allele fraction, respectively, indicating a high recurrence risk. Grandparental studies revealed that the deletion arose on the mother's paternal chromosome 16. PGT studies revealed 44% embryos with the deletion, reflecting high-level germline mosaicism.CONCLUSION:
Our data further demonstrate the importance of parental testing in ACDMPV families and reproductive usefulness of IVF with PGT in families with high-level parental gonosomal mosaicism.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Persistent Fetal Circulation Syndrome
Limits:
Female
/
Humans
/
Infant
/
Newborn
Language:
En
Journal:
Mol Genet Genomic Med
Year:
2022
Document type:
Article
Affiliation country:
United States