A novel surfactant protein C gene mutation associated with progressive respiratory failure in infancy

Area of Science:

• Pulmonary Medicine
• Genetics
• Pediatric Respiratory Diseases

Background:

• Mutations in the Surfactant Protein C (SPC) gene (SFTPC) are linked to childhood interstitial lung disease (chILD).
• Clinical presentation, severity, and outcomes of SFTPC-related chILD vary significantly.
• Limited data exists on the specific outcomes for infants with SFTPC mutations.

Purpose of the Study:

• To report a novel SFTPC mutation associated with severe infantile chILD.
• To systematically review SFTPC mutations in the literature to define clinical features and outcomes.
• To improve understanding and management of SFTPC-related chILD in infants.

Main Methods:

• Case report of a novel SFTPC mutation (c.435G->A, p.(Gln145)) in an infant with severe respiratory failure.
• Analysis of SP-C transcripts to identify molecular mechanisms, including exon skipping.
• Systematic literature review of all reported SFTPC mutations in chILD.

Main Results:

• The novel mutation led to early-onset symptoms, progressive respiratory failure, mechanical ventilation, and lung transplant at one year.
• Transcript analysis revealed exon 4 skipping, despite the mutation not being predicted to alter the amino acid sequence.
• The systematic review aimed to consolidate presenting features, clinical/radiologic findings, and outcomes for SFTPC mutations.

Conclusions:

• Novel SFTPC mutations can cause severe, early-onset chILD requiring intensive medical intervention.
• Understanding the molecular consequences of SFTPC mutations, like exon skipping, is crucial.
• Further research and international registries are needed to better track and manage patients with SFTPC-related chILD.