Gene variants of the phosphatidylcholine synthesis pathway do not contribute to RDS in the Chinese population.

Background: To determine population-based prevalence and disease contribution of phosphatidylcholine synthetic pathway-associated gene variants in a native southern Chinese cohort.

Methods: We used bloodspots from 2010 that were obtained from the Guangxi Neonatal Screening Center in Nannning China and included the Han (n = 443) and Zhuang (n = 313) ethnic groups. We sequenced the exons of cholinephosphate cytidylyltransferase (PCYT1B) lysophospholipid acyltransferase 1 (LPCAT1), and cholinephosphotransferase (CHPT1) genes, and analyzed both rare and common exonic variants.

Population-based frequency of surfactant dysfunction mutations in a native Chinese cohort.

Background: Rare mutations in surfactant-associated genes contribute to neonatal respiratory distress syndrome. The frequency of mutations in these genes in the Chinese population is unknown.

Methods: We obtained blood spots from the Guangxi Neonatal Screening Center in Nanning, China that included Han (n=443) and Zhuang (n=313) ethnic groups.

[Pulmonary surfactant associated gene variants in mixed ethnic population of Han and Zhuang].

Objective: To explore the prevalence of pulmonary surfactant associated pathway genes functional variants in Chinese population.

Method: Using a cohort of 258 mixed ethnic population of Han and Zhuang, we pooled DNA samples from 146 term male infants and 112 term female infants and then used an Ill umina next generation sequencing platform to perform the complete exonic resequencing in 6 target genes:surfactant protein-B (SFTPB), surfactant protein-C (SFTPC), ATP-binding cassette transporter A3 (ABCA3), lysophospholipid acyltransferase 1 (LPCAT1), choline phosphotransferase 1 (CHPT1), phosphate cytidylyltransferase 1, choline, beta (PCYT1B). Collapsing methods was used to determine the functional allele frequency.

Single ABCA3 mutations increase risk for neonatal respiratory distress syndrome.

Background And Objective: Neonatal respiratory distress syndrome (RDS) due to pulmonary surfactant deficiency is heritable, but common variants do not fully explain disease heritability.

Methods: Using next-generation, pooled sequencing of race-stratified DNA samples from infants ≥34 weeks' gestation with and without RDS (n = 513) and from a Missouri population-based cohort (n = 1066), we scanned all exons of 5 surfactant-associated genes and used in silico algorithms to identify functional mutations. We validated each mutation with an independent genotyping platform and compared race-stratified, collapsed frequencies of rare mutations by gene to investigate disease associations and estimate attributable risk.

Inherited surfactant deficiency caused by uniparental disomy of rare mutations in the surfactant protein-B and ATP binding cassette, subfamily a, member 3 genes.

Objective: To characterize inheritance of homozygous, rare, recessive loss-of-function mutations in surfactant protein-B (SFTPB) or ATP binding cassette, subfamily A, member 3 (ABCA3) genes in newborns with lethal respiratory failure.

Study Design: We resequenced genes from parents whose infants were homozygous for mutations in SFTPB or ABCA3. For infants with only 1 heterozygous parent, we performed microsatellite analysis for chromosomes 2 (SFTPB) and 16 (ABCA3).