Pediatric Pulmonology 9999:1–12 (2016) Review A Novel Surfactant Protein C Gene Mutation Associated With Progressive Respiratory Failure in Infancy Melissa Kaori Silva Litao, MD, 1 Don Hayes Jr., MD, MS, 2 Saurabh Chiwane, MD, 3 Lawrence M. Nogee, MD, 4 Geoffrey Kurland, MD, 5 and Lokesh Guglani, MD, FAAP 6 * Summary. Mutations of the Surfactant Protein C (SPC) gene (SFTPC) have been associated with childhood interstitial lung disease (chILD) with variable age of onset, severity of lung disease, and outcomes. We report a novel mutation in SFTPC [c.435G->A, p.(Gln145)] that was associated with onset of symptoms in early infancy, progressive respiratory failure with need for prolonged mechanical ventilatory support, and eventual lung transplant at 1 year of age. While the mutation was not predicted to alter the amino acid sequence of the SP-C precursor protein, analysis of SP-C transcripts demonstrated skipping of exon 4. Because of limited data about the outcomes of infants with SFTPC mutations, we conducted a systematic review of all the SFTPC mutations reported in the literature in order to define their presenting features, clinical and radiologic features, and outcomes. Further advances in our understanding of chILD and creation of an international registry will help to track these patients and their outcomes. Pediatr Pulmonol. 2016; 9999:XX–XX. ß 2016 Wiley Periodicals, Inc. Key words: respiratory failure; surfactant; mutation; infant; transplant; lung; interstitial; chest. Funding source: none reported. 1 Department of Pediatrics, Children’s Hospital of Michigan, Detroit, Michigan. 2 Section of Pulmonary Medicine, Lung Transplant Program, Nationwide Children’s Hospital, The Ohio State University, Columbus, Ohio. 3 Division of Pediatric Critical Care, Department of Pediatrics, Children’s Hospital of Michigan, Detroit, Michigan. 4 Eudowood Neonatal Pulmonary Division, Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland. 5 Division of Pulmonary Medicine Allergy and Immunology, Department of Pediatrics, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania. 6 Division of Pulmonology, Allergy/Immunology, Cystic Fibrosis and Sleep (PACS), Department of Pediatrics, Children’s Healthcare of Atlanta, Atlanta, Georgia 30322. Conflict of interest: None. Disclosure: The corresponding author was involved in the diagnosis and management of the index case while working at Children’s Hospital of Michigan. The protocol for the systematic review was registered with the International Prospective Register of Systematic Reviews (maintained by University of York Center for Reviews and Dissemination, at http://www.crd.york.ac.uk/PROSPERO/) (Protocol #CRD42016035437).  Correspondence to: Lokesh Guglani, MD, FAAP, Emory Children’s Center, 2015 Uppergate Drive, Room 348, Atlanta, GA 30322. E-mail: lokesh.guglani@emory.edu Received 25 February 2016; Revised 25 March 2016; Accepted 6 May 2016. DOI 10.1002/ppul.23493 Published online in Wiley Online Library (wileyonlinelibrary.com). ß 2016 Wiley Periodicals, Inc.