RESUMO
BACKGROUND: Whole-exome sequencing (WES) has become an invaluable tool for genetic diagnosis in paediatrics. However, it has not been widely adopted in the prenatal setting. This study evaluated the use of WES in prenatal genetic diagnosis in fetuses with structural congenital anomalies (SCAs) detected on prenatal ultrasound. METHOD: Thirty-three families with fetal SCAs on prenatal ultrasonography and normal chromosomal microarray results were recruited. Genomic DNA was extracted from various fetal samples including amniotic fluid, chorionic villi, and placental tissue. Parental DNA was extracted from peripheral blood when available. We used WES to sequence the coding regions of parental-fetal trios and to identify the causal variants based on the ultrasonographic features of the fetus. RESULTS: Pathogenic mutations were identified in three families (n = 3/33, 9.1%), including mutations in DNAH11, RAF1 and CHD7, which were associated with primary ciliary dyskinesia, Noonan syndrome, and CHARGE syndrome, respectively. In addition, variants of unknown significance (VUSs) were detected in six families (18.2%), in which genetic changes only partly explained prenatal features. CONCLUSION: WES identified pathogenic mutations in 9.1% of fetuses with SCAs and normal chromosomal microarray results. Databases for fetal genotype-phenotype correlations and standardized guidelines for variant interpretation in prenatal diagnosis need to be established to facilitate the use of WES for routine testing in prenatal diagnosis.
Assuntos
Síndrome CHARGE/genética , Transtornos da Motilidade Ciliar/genética , Sequenciamento do Exoma , Síndrome de Noonan/genética , Líquido Amniótico/metabolismo , Dineínas do Axonema/genética , Síndrome CHARGE/diagnóstico , Transtornos da Motilidade Ciliar/diagnóstico , DNA/isolamento & purificação , DNA/metabolismo , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Feminino , Feto/metabolismo , Humanos , Síndrome de Noonan/diagnóstico , Fenótipo , Placenta/metabolismo , Gravidez , Diagnóstico Pré-Natal , Proteínas Proto-Oncogênicas c-raf/genética , Ultrassonografia Pré-NatalRESUMO
OBJECTIVES: To determine the prevalence of maternal colonization with group B streptococcus (GBS), and early onset GBS disease (EOGBSD) after implementation of universal screening. METHODS: This was a three-year retrospective cohort study on universal antenatal rectovaginal culture-based screening and intrapartum antimicrobial prophylaxis (IAP) to colonized women in the public sector in Hong Kong. Routinely collected data including maternal colonization and EOGBSD were retrieved. RESULTS: Of 113,989 GBS screening performed, 21.8% were positive. The colonization rate was higher in the public hospitals (higher risk) than in the Maternal and Child Health Centers (lower risk) (23.7% vs 18.1%, p < .001), while their false negative rates were not greater than expected. Majority of eligible women opted for screening, and colonized women received IAP. There were 29 cases of EOGBSD with clinical signs and a positive blood or cerebrospinal fluid culture. Compared to clinical risk-based screening, EOGBSD incidence decreased after universal screening (1 vs 0.24 per 1000 births, p < .001). Although EOGBSD occurred at a higher rate in preterm than term infants, 86.7% occurred in the latter, and were associated with a false negative screening result (41.3%), lack of screening (20.7%) or unavailability of a colonization result at labour (13.8%). CONCLUSIONS: Maternal GBS colonization rate was higher than previously reported, and varied with different risk populations. EOGBSD reduced after universal screening.