title: Development and validation of a fetal genotyping assay with potential for noninvasive prenatal diagnosis of hereditary hearing loss.
abstract: OBJECTIVE
  Inherited non-syndromic hearing loss (NSHL) is a common sensory disorder that afflicts otherwise healthy individuals. The aim of the study was to evaluate the performance of circulating single molecule amplification and re-sequencing technology (cSMART) for non-invasive prenatal testing (NIPT) of NSHL.
  
  
  METHODS
  Neonatal inheritance of NSHL mutations was determined from bloodspots using SNaPshot genotyping. NIPT of cell-free DNA for fetal NSHL mutations in the GJB2, GJB3 and SLC26A4 genes was performed by a multiplex cSMART assay. The percentage of mutant alleles was used to deduce fetal DNA fractions and assign fetal genotypes.
  
  
  RESULTS
  A total of 25 plasma samples selected with different fetal NSHL genotypes were coded and retrospectively analyzed by NIPT. Three normal fetuses, 18 carrier fetuses comprising seven GJB2 109G>A, four GBJ2 235delC, three GJB2 299-300delAT and four SLC26A4 IVS7-2A>G heterozygotes and four affected fetuses comprising two GJB2 109G>A homozygotes, one GBJ2 235delC homozygote and one compound GJB2 235delC/299-300delAT heterozygote were identified. All 25 fetal genotypes determined by the cSMART assay were concordant with neonatal genotypes.
  
  
  CONCLUSIONS
  The cSMART assay applied to cell-free DNA isolated from maternal plasma of pregnant women is highly accurate for calling correct fetal NSHL genotypes. © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Central Lab, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu, China.|Nanjing Medical University Affiliated Wuxi Maternity and Child Health Care Hospital, Wuxi, Jiangsu, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Berry Genomics Corporation, Beijing, China.
authors.forename: Yiqian
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Gynecology Department, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu, China.
authors.forename: Benjing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Central Lab, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu, China.|Obstetrics Department, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Mao
authors.affiliation: Center for Reproduction and Genetics, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Child Health Care Department, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu, China.
authors.forename: Kan
authors.initials: K
authors.lastname: Ye
authors.affiliation: Child Health Care Department, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu, China.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Berry Genomics Corporation, Beijing, China.
authors.forename: David S
authors.initials: DS
authors.lastname: Cram
authors.affiliation: Center for Reproduction and Genetics, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
mesh_terms: D000072259:Connexin 26 / Q000235:genetics; D017630:Connexins / Q000235:genetics; D004247:DNA / Q000097:blood; D005260:Female; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods*; D034381:Hearing Loss / Q000151:congenital* / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D026901:Membrane Transport Proteins / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D000076988:Sulfate Transporters
chemical_list: D017630:Connexins; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26; C068044:GJB3 protein, human; D004247:DNA