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A Novel Mutation in FOXF1 Gene Associated with a Delayed Presentation of Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins

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DOI: 10.4236/crcm.2015.43021    2,661 Downloads   2,965 Views  

ABSTRACT

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, fatal developmental lung disorder of neonates and infants, associated with severe persistent pulmonary hypertension unresponsive to treatment. We reported the case of a term newborn with delayed presentation of ACD/MPV and a novel mutation of FOXF1 gene that received supportive cardiopulmonary treatments, inhaled nitric oxide, oral sildenafil and nebulized iloprost with no clinical improvement. DNA sequence analysis of FOXF1 gene identified a novel heterozygous variant c.257G > C; p.R86P, in exon 1. At autopsy, lung histology showed the characteristic features of ACD/MPV. FOXF1 has been identified as one of the genes responsible for ACD/MPV associated with multiple congenital malformations. This is a report of a novel heterozygous variant c.257G > C; p.R86P, in the first exon of FOXF1, in a patient with delayed presentation of ACD/MPV.

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Eikani, M. , Kalinichenko, V. , Pradhan, A. and Noe, J. (2015) A Novel Mutation in FOXF1 Gene Associated with a Delayed Presentation of Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins. Case Reports in Clinical Medicine, 4, 97-101. doi: 10.4236/crcm.2015.43021.

References

[1] Bishop, N.B., Stankiewicz, P. and Steinhorn, R.H. (2011) Alveolar Capillary Dysplasia. American Journal of Respiratory and Critical Care Medicine, 184, 172-179.
http://dx.doi.org/10.1164/rccm.201010-1697CI
[2] Sen, P., Thakur, N., Stockton, D.W., Langston, C. and Bejjani, B. (2004) Expanding the Phenotype of Alveolar Capillary Dysplasia (ACD). The Journal of Pediatrics, 145, 646-651.
http://dx.doi.org/10.1016/j.jpeds.2004.06.081
[3] Sen, P., Yang, Y., Navarro, C., Silva, I., Szafranski, P., Kolodziejska, K.E., et al. (2013) Novel FOXF1 Mutations in Sporadic and Familial Cases of Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins Imply a Role for Its DNA Binding Domain. Human Mutation, 34, 801-811.
http://dx.doi.org/10.1002/humu.22313
[4] Ahmed, S., Ackerman, V., Faught, P. and Langston, C. (2008) Profound Hypoxemia and Pulmonary Hypertension in a 7-Month-Old Infant: Late Presentation of Alveolar Capillary Dysplasia. Pediatric Critical Care Medicine, 9, e43-e46.
http://dx.doi.org/10.1097/PCC.0b013e31818e383e
[5] Abdallah, H.I., Karmazin, N. and Marks, L.A. (1993) Late Presentation of Misalignment of Lung Vessels with Alveolar Capillary Dysplasia. Critical Care Medicine, 21, 628-630.
http://dx.doi.org/10.1097/00003246-199304000-00026
[6] Shankar, V., Haque, A., Johnson, J. and Pietsch, J. (2006) Late Presentation of Alveolar Capillary Dysplasia in an Infant. Pediatric Critical Care Medicine, 7, 177-179.
http://dx.doi.org/10.1097/01.PCC.0000202570.58016.67
[7] Shehata, B.M. and Abramowsky, C.R. (2005) Alveolar Capillary Dysplasia in an Infant with Trisomy 21. Pediatric and Developmental Pathology, 8, 696-700.
http://dx.doi.org/10.1007/s10024-005-2137-6
[8] Fisher, J.C., Stolar, C.J.H. and Cowles, R.A. (2008) Extracorporeal Membrane Oxygenation for Cardiopulmonary Failure in Pediatric Patients: Is a Second Course Justified? Journal of Surgical Research, 148, 100-108.
http://dx.doi.org/10.1016/j.jss.2008.03.023
[9] Antao, B., Samuel, M., Kiely, E., Spitz, L. and Malone, M. (2006) Congenital Alveolar Capillary Dysplasia and Associated Gastrointestinal Anomalies. Fetal & Pediatric Pathology, 25, 137-145.
http://dx.doi.org/10.1080/15513810600908230
[10] Bishop, N., Stankiewicz, P. and Steinhorn, R. (2011) Alveolar Capillary Dysplasia. American Journal of Respiratory and Critical Care Medicine, 184, 172-179.
http://dx.doi.org/10.1164/rccm.201010-1697CI
[11] Mahlapuu, M., Enerback, S. and Carlsson, P. (2001) Haploinsufficiency of the Forkhead Gene Foxf1, a Target for Sonic Hedgehog Signaling, Causes Lung and Foregut Malformations. Development, 128, 2397-2406.
[12] Kalinichenko, V.V., Gusarova, G.A., Kim, I.M., Shin, B., Yoder, H.M., Clark, J., Sapozhnikov, A.M., Whitsett, J.A. and Costa, R.H. (2004) Foxf1 Haploinsufficiency Reduces Notch-2 Signaling during Mouse Lung Development. American Journal of Physiology—Lung Cellular and Molecular, 286, L521-L530.
http://dx.doi.org/10.1152/ajplung.00212.2003
[13] Kalinichenko, V.V., Gusarova, G.A., Shin, B., Costa, R.H. (2003) The Forkhead Box F1 Transcription Factor Is Expressed in Brain and Head Mesenchyme during Mouse Embryonic Development. Gene Expression Patterns, 3, 153-158.
http://dx.doi.org/10.1016/S1567-133X(03)00010-3
[14] Kalinichenko, V.V., Bhattacharyya, D., Zhou, Y., Gusarova, G.A., Kim, W., Shin, B. and Costa, R.H. (2002) Foxf1 +/- Mice Exhibit Defective Stellate Cell Activation and Abnormal Liver Regeneration Following CCl4 Injury. Hepatology, 37, 107-117.
http://dx.doi.org/10.1053/jhep.2003.50005
[15] Stankiewicz, P., Sen, P., Bhatt, S., Storer, M., Xia, Z., Bejjani, B.A., et al. (2009) Genomic and Genetic of the FOX Gene Cluster on 16q24.1 and Inactivating Mutations of the FOXF1 Cause Alveolar Capillary Dysplasia and Other Malformations. American Journal of Human Genetics, 84, 780-791.
http://dx.doi.org/10.1016/j.ajhg.2009.05.005

  
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