OBJECTIVES: The implementation of chromosomal microarray analysis (CMA) in prenatal testing for all patients has not achieved a consensus. Technical alternatives such as Prenatal BACs-on-Beads(TM) (PNBoBs(TM) ) have thus been applied. The aim of this study was to provide the frequencies of the submicroscopic defects detectable by PNBoBs(TM) under different prenatal indications. METHODS: A total of 9648 prenatal samples were prospectively analyzed by karyotyping plus PNBoBs(TM) and classified by prenatal indication. The frequencies of the genomic defects and their 95%CIs were calculated for each indication. RESULTS: The overall incidence of cryptic imbalances was 0.7%. The majority involved the DiGeorge syndrome critical region (DGS). The additional diagnostic yield of PNBoBs(TM) in the population with a low a priori risk was 1/298. The prevalences of DGS microdeletion and microduplication in the low-risk population were 1/992 and 1/850, respectively. CONCLUSIONS: The constant a priori risk for common pathogenic cryptic imbalances detected by this technology is estimated to be ~0.3%. A prevalence higher than that previously estimated was found for the 22q11.2 microdeletion. Their frequencies were independent of maternal age. These data have implications for cell-free DNA screening tests design and justify prenatal screening for 22q11 deletion, as early recognition of DGS improves its prognosis.
OBJECTIVES: The implementation of chromosomal microarray analysis (CMA) in prenatal testing for all patients has not achieved a consensus. Technical alternatives such as Prenatal BACs-on-Beads(TM) (PNBoBs(TM) ) have thus been applied. The aim of this study was to provide the frequencies of the submicroscopic defects detectable by PNBoBs(TM) under different prenatal indications. METHODS: A total of 9648 prenatal samples were prospectively analyzed by karyotyping plus PNBoBs(TM) and classified by prenatal indication. The frequencies of the genomic defects and their 95%CIs were calculated for each indication. RESULTS: The overall incidence of cryptic imbalances was 0.7%. The majority involved the DiGeorge syndrome critical region (DGS). The additional diagnostic yield of PNBoBs(TM) in the population with a low a priori risk was 1/298. The prevalences of DGS microdeletion and microduplication in the low-risk population were 1/992 and 1/850, respectively. CONCLUSIONS: The constant a priori risk for common pathogenic cryptic imbalances detected by this technology is estimated to be ~0.3%. A prevalence higher than that previously estimated was found for the 22q11.2 microdeletion. Their frequencies were independent of maternal age. These data have implications for cell-free DNA screening tests design and justify prenatal screening for 22q11 deletion, as early recognition of DGS improves its prognosis.
Authors: Wolfram Demaerel; Matthew S Hestand; Elfi Vergaelen; Ann Swillen; Marcos López-Sánchez; Luis A Pérez-Jurado; Donna M McDonald-McGinn; Elaine Zackai; Beverly S Emanuel; Bernice E Morrow; Jeroen Breckpot; Koenraad Devriendt; Joris R Vermeesch Journal: Am J Hum Genet Date: 2017-09-28 Impact factor: 11.025
Authors: Lisa D Palmer; Nancy J Butcher; Erik Boot; Kathleen A Hodgkinson; Tracy Heung; Eva W C Chow; Alina Guna; T Blaine Crowley; Elaine Zackai; Donna M McDonald-McGinn; Anne S Bassett Journal: Am J Med Genet A Date: 2018-04 Impact factor: 2.802
Authors: Arpana Rayannavar; Lorraine E Levitt Katz; Terrence Blaine Crowley; Megan Lessig; Katheryn Grand; Elizabeth Goldmuntz; Elaine H Zackai; Donna M McDonald-McGinn Journal: Am J Med Genet A Date: 2018-10-01 Impact factor: 2.802
Authors: Donna M McDonald-McGinn; Kathleen E Sullivan; Bruno Marino; Nicole Philip; Ann Swillen; Jacob A S Vorstman; Elaine H Zackai; Beverly S Emanuel; Joris R Vermeesch; Bernice E Morrow; Peter J Scambler; Anne S Bassett Journal: Nat Rev Dis Primers Date: 2015-11-19 Impact factor: 52.329