Synonymous ABCA3 Variants Do Not Increase Risk for Neonatal Respiratory Distress Syndrome

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• 作者：Jennifer A. Wambach ; MD ; MS¹ ; ^{wambach_j@kids.wustl.edu" class="auth_mail} ; Daniel J. Wegner ; MS¹ ; Hillary B. Heins ; BS¹ ; Todd E. Druley ; MD ; PhD¹ ; ² ; Robi D. Mitra ; PhD² ; Aaron Hamvas ; MD¹ ; F. Sessions Cole ; MD¹
• 关键词：ABCA3 ; Adenosine triphosphate-binding cassette A3 transporter ; ESP ; Exome Sequencing Project ; MAF ; Minor allele frequency ; RDS ; Respiratory distress syndrome
• 刊名：The Journal of Pediatrics
• 出版年：June 2014
• 年：2014
• 卷：164
• 期：6
• 页码：1316-1321.e3
• 全文大小：197 K

文摘

To determine whether synonymous variants in the adenosine triphosphate-binding cassette A3 transporter (ABCA3) gene increase the risk for neonatal respiratory distress syndrome (RDS) in term and late preterm infants of European and African descent.

Study design

Using next-generation pooled sequencing of race-stratified DNA samples from infants of European and African descent at ≥34 weeks gestation with and without RDS (n = 503), we scanned all exons of ABCA3, validated each synonymous variant with an independent genotyping platform, and evaluated race-stratified disease risk associated with common synonymous variants and collapsed frequencies of rare synonymous variants.

Results

The synonymous ABCA3 variant frequency spectrum differs between infants of European descent and those of African descent. Using in silico prediction programs and statistical strategies, we found no potentially disruptive synonymous ABCA3 variants or evidence of selection pressure. Individual common synonymous variants and collapsed frequencies of rare synonymous variants did not increase disease risk in term and late-preterm infants of European or African descent.

Conclusion

In contrast to rare, nonsynonymous ABCA3 mutations, synonymous ABCA3 variants do not increase the risk for neonatal RDS among term and late-preterm infants of European or African descent.