Haploinsufficiencies of FOXF1 and FOXC2 genes associated with lethal alveolar capillary dysplasia and congenital heart disease.
Neonatal deaths account for about 67% of all deaths during the first year of life in the USA. Genetic defects are important factors contributing to neonatal deaths and congenital anomalies. Here we report on the identification of a 1.37 Mb de novo deletion of chromosome 16q24.1-q24.2 by microarray-based comparative genomic hybridization (aCGH) technique in a newborn boy with lethal severe alveolar capillary dysplasia and multiple congenital anomalies who died of irreversible pulmonary hypertension, respiratory failure and cor pulmonale at three days of age. The phenotypic findings and causal genes (FOXF1 and FOXC2) involved in producing this unusual syndrome are detailed. Our findings independently confirm the results in a previous publication describing multiple patients with similar clinical and genetic observations, and highlight the importance of scanning human genomes at high resolution for identifications of micro-imbalances as pathogenic causes in neonates with unexplained congenital anomalies. (c) 2010 Wiley-Liss, Inc.
Yu
Shihui
S
Children's Mercy Hospitals and Clinics and University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108, USA.
Shao
Lei
L
Kilbride
Howard
H
Zwick
David L
DL
D002196:Capillaries / Q000002:abnormalities*; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000235:genetics*; D018628:Gene Dosage / Q000235:genetics; D006238:Haploidy; D006330:Heart Defects, Congenital / Q000150:complications* / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010290:Parents; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000002:abnormalities* / Q000473:pathology; D015203:Reproducibility of Results
C098521:FOXF1 protein, human; D051858:Forkhead Transcription Factors; C082078:mesenchyme fork head 1 protein