A quantitative cSMART assay for noninvasive prenatal screening of autosomal recessive nonsyndromic hearing loss caused by GJB2 and SLC26A4 mutations

作者：Han, Mingyu; Li, Zhifeng; Wang, Wenlu; Huang, Shasha; Lu, Yanping; Gao, Zhiying; Wang, Longxia; Kang, Dongyang; Li, Linwei; Liu, Yiqian; Xu, Mengnan; Cram, David S.^*; Dai, Pu^*

来源：Genetics in Medicine, 2017, 19(12): 1309-1316.

DOI：10.1038/gim.2017.54

• autosomal recessive nonsyndromic hearing loss (ARNSHL)
• cell free plasma DNA
• circulating single-molecule amplification and resequencing technology (cSMART)
• fetal DNA fraction
• noninvasive prenatal screening (NIPS)

Purpose: The aim of this study was to assess the performance of a noninvasive prenatal screening (NIPS) assay for accurate fetal genotyping of pregnancies at genetic risk for autosomal recessive nonsyndromic hearing loss (ARNSHL). @@@ Methods: A total of 80 pregnant couples carrying known mutations in either the GJB2 or SLC26A4 genes associated with a risk for ARNSHL were recruited to the study. Fetal amniocyte samples were genotyped by invasive prenatal screening (IPS), whereas the cell-free fetal DNA present in maternal plasma samples was genotyped using a novel NIPS method based on circulating single-molecule amplification and resequencing technology (cSMART). @@@ Results: IPS of the 80 at-risk pregnancies identified 20 normal homozygote, 42 heterozygote, 5 affected homozygote, and 13 affected compound heterozygote fetuses. Benchmarking against IPS, 73 of 80 fetuses (91.3%) were correctly genotyped by the cSMART NIPS assay. A low fetal DNA fraction (<6%) was identified as the main contributing factor in five of seven discordant NIPS results. At fetal DNA fractions >6%, the sensitivity and specificity of the cSMART assay for correctly diagnosing ARNSHL were 100 and 96.5%, respectively. @@@ Conclusion: Based on key performance indicators, the cSMART NIPS assay has clinical potential as an alternative to traditional IPS of ARNSHL.

• 出版日期2017-12
• 单位中国人民解放军总医院