Whole-exome sequencing in fetuses with central nervous system abnormalities

Objectivewe describe our experience with whole-exome sequencing (wes) in fetuses with central nervous system (cns) abnormalities following a normal chromosomal microarray result.methodsduring the study period (2014–2017) 7 cases (9 fetuses) with prenatally diagnosed cns abnormality, whose chromosomal microarray analysis was negative, were offered whole-exome sequencing analysis.resultsa pathogenic or a likely pathogenic variant was found in 5 cases including a previously described, likely pathogenic de novo tuba1a variant (case #1); a previously described homozygous vrk1 variant (case #2); an x-linked arx variant (case #3); a likely pathogenic heterozygous variant in the tubb3 gene (case #5). finally, in two fetuses of the same couple (case #6), a compound heterozygous state was detected, consisting of the nphp1 gene deletion and a sequence variant of uncertain significance. two additional cases had normal wes results.conclusionwhole-exome sequencing may improve prenatal diagnosis in fetuses with cns abnormalities.