A Novel De Novo Pathogenic Variant in FOXF1 in a Newborn with Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins.
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is an autosomal dominant, fatal developmental disorder of the lungs, with a mortality rate of about 100%. ACD/MPV is caused by mutations in FOXF1. Herein, we describe a newborn boy with ACD/MPV carrying a novel pathogenic variant of FOXF1. The patient developed respiratory distress and severe pulmonary hypertension on the first day of life. Despite aggressive cardiorespiratory management, including veno-venous extracorporeal membrane oxygenation, his condition deteriorated rapidly, and he died within the first month of his life. Lung histology showed the characteristic features of ACD/MPV at autopsy. Sequence analysis of FOXF1 from genomic DNA obtained from autopsied lung tissue revealed that the patient was heterozygous for a novel missense variant (c.305T>C; p.Leu102Pro). Further analysis of both parents confirmed the de novo occurrence of the variant. To the best of our knowledge, this is the first report of genetically confirmed ACD/MPV in Korea.
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Youngeun
Y
Ma
Department of Laboratory Medicine and Genetics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea.
Mi Ae
MA
Jang
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Hye Soo
HS
Yoo
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
So Yoon
SY
Ahn
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Se In
SI
Sung
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Yun Sil
YS
Chang
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. changski@skku.edu.
Chang Seok
CS
Ki
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. wonspark@skku.edu.
Won Soon
WS
Park
D004252:DNA Mutational Analysis; D051858:Forkhead Transcription Factors / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000473:pathology*; D008297:Male; D009154:Mutation; D020125:Mutation, Missense / Q000235:genetics*; D010547:Persistent Fetal Circulation Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D011650:Pulmonary Alveoli / Q000002:abnormalities*; D011667:Pulmonary Veins / Q000002:abnormalities*; D056910:Republic of Korea; D017421:Sequence Analysis
D051858:Forkhead Transcription Factors
Alveolar capillary dysplasia with misalignment of pulmonary veins; FOXF1; Korean; pathogenic; variant