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

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

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.

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.

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.