Genetic basis of surfactant dysfunction in Chinese children: A retrospective study

Objective: To investigate the prevalence of surfactant dysfunction (SD) and the genotype distribution in Chinese childhood interstitial lung disease (chILD).

Methods: From December 2013 to December 2016, whole exons and splicing regions of surfactant protein (SP)-B, SP-C, and adenosine triphosphate (ATP)-binding cassette subfamily A member 3 (ABCA3) were sequenced in chILD with unknown etiology in five children's medical centers of China. The sequencing was performed by Next-generation sequencing technique in a molecular genetics laboratory. The clinical and genetic data were reviewed retrospectively.

Results: In total, 136 patients of age 3 months to 13 years (mean 12.5 ± 9.4 months) were recruited, among which 76 were males. Of the 136 cases of chILD, 13.2% (18 of 136) were diagnosed with SD. In these 18 SD cases, 15 had heterozygous SP-C deficiencies, two cases had compound heterozygous ABCA3 deficiencies, and no SP-B deficiency was identified. In SP-C deficiencies, there were six cases with p.I73T, 2 with p.I73N, 5 with p.V39L, 1 with c.417delA, and 1 case with IVS4, +1G>C. Two cases of ABCA3 mutation were heterozygous with c.1755delC and c.2890G>A; c.3913T>C (R1305W) and exon 13 to 18 deletion. One was negative by sequencing while diagnosed positive by pathology.

Conclusion: The proportion of genetic mutation of SD in chILD is 13.2% in China, of which SP-C deficiency is predominant. The mutation, SP-C p.V39L, was found to be relatively prevalent in China and warrants further investigation.