OBJECTIVE: To investigate the genetic characteristics and cause of death for an infant with alveolar capillary dysplasia and pulmonary vein misalignment (ACD/MPV). METHODS: An infant with ACD/MPV diagnosed at the Affiliated Maternity and Child Health Care Hospital of Nantong University in September 2022 was selected as the study subject. Clinical data of the infant were collected. Whole exome sequencing (WES) was carried out to detect genetic variants in the skin tissue, and Sanger sequencing was performed for verifying the candidate variants in the parents. Droplet digital PCR (ddPCR) was used to determine the mosaicism ratio of the variant in different germ layer-derived samples from the father. RESULTS: The infant had died within 2 days after birth due to hypoxemia and respiratory distress. WES revealed that she has harbored a c.433C>T nonsense variant in exon 1 of the FOXF1 gene, which was unreported previously. Sanger sequencing has verified the variant in the infant, with her mother's locus being the wild-type and a minor variant peak noted in her father. ddPCR indicated that the mosaic ratio of the c.433C>T variant in the father's sperm was 27.18%, with the mosaic ratios of the variant in tissues originating from the three germ layers ranging from 11% to 28%. CONCLUSION The c.433C>T variant derived from the paternal germline and somatic mosaicism of the FOXF1 gene had probably predisposed to the neonatal death of this infant. ddPCR is an effective method for detecting mosaic variants.
Female ; Humans ; Pregnancy ; Child ; Infant ; Infant, Newborn ; Male ; Semen ; Infant Death ; Exons ; Mosaicism ; Forkhead Transcription Factors/genetics*

OBJECTIVE: To explore the genetic basis of cerebral palsy (CP). METHODS: A pair of twins with cerebral palsy and different phenotypes were subjected to whole genome sequencing, and other 8 children with CP were subjected to whole exome sequencing. Genetic variations were screened by a self-designed filtration process in order to explore the CP-related biological pathways and genes. RESULTS: Three biological pathways related to CP were identified, which included axon guiding, transmission across chemical synapses and protein-protein interactions at synapses, and 25 susceptibility genes for CP were identified. CONCLUSION The molecular mechanism of CP has been explored, which may provide clues for development of new treatment for CP.
Cerebral Palsy ; genetics ; Child ; Genetic Testing ; Humans ; Phenotype ; Whole Exome Sequencing ; Whole Genome Sequencing