A Novel De Novo Pathogenic Variant in FOXF1 in a Newborn with Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins

• Published in: Yonsei medical journal Vol. 58; no. 3; pp. 672 - 675
• Main Authors: Ma, Youngeun, Jang, Mi-Ae, Yoo, Hye Soo, Ahn, So Yoon, Sung, Se In, Chang, Yun Sil, Ki, Chang-Seok, Park, Won Soon
• Format: Journal Article
• Language: English
• Published: Korea (South) Yonsei University College of Medicine 01.05.2017; 연세대학교의과대학
• Subjects: Case Report; DNA Mutational Analysis; Forkhead Transcription Factors - genetics; Genetic Predisposition to Disease; Heterozygote; Humans; Infant, Newborn; Lung - pathology; Male; Mutation; Mutation, Missense - genetics; Persistent Fetal Circulation Syndrome - diagnosis; Persistent Fetal Circulation Syndrome - genetics; Persistent Fetal Circulation Syndrome - therapy; Pulmonary Alveoli - abnormalities; Pulmonary Veins - abnormalities; Republic of Korea; Sequence Analysis; 의학일반; variant; Alveolar capillary dysplasia with misalignment of pulmonary veins; Korean; pathogenic; FOXF1
• ISSN: 0513-5796; 1976-2437; 1976-2437
• DOI: 10.3349/ymj.2017.58.3.672

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.