For CMA to be maximally useful in prenatal diagnosis, parental DNA samples as well as robust datasets to provide predictive phenotypic information are required. The most common reason for undertaking CMA was to evaluate an ultrasound anomaly, and benign familial variants were a common finding. Genetic services are required to provide pre- and post-test genetic counseling and help families interpret results.

No abstract

The 22q11.2 deletion syndrome (22q11DS) affects 1:4000 live births and presents with highly variable phenotype expressivity. In this study, we developed an analytical approach utilizing whole genome sequencing and integrative analysis to discover genetic modifiers. Our pipeline combined available tools in order to prioritize rare, predicted deleterious, coding and non-coding single nucleotide variants (SNVs) and insertion/deletions (INDELs) from whole genome sequencing (WGS). We sequenced two unrelated probands with 22q11DS, with contrasting clinical findings, and their unaffected parents. Proband P1 had cognitive impairment, psychotic episodes, anxiety, and tetralogy of Fallot (TOF); while proband P2 had juvenile rheumatoid arthritis but no other major clinical findings. In P1, we identified common variants in COMT and PRODH on 22q11.2 as well as rare potentially deleterious DNA variants in other behavioral/neurocognitive genes. We also identified a de novo SNV in ADNP2 (NM_014913.3:c.2243G>C), encoding a neuroprotective protein that may be involved in behavioral disorders. In P2, we identified a novel non-synonymous SNV in ZFPM2 (NM_012082.3:c.1576C>T), a known causative gene for TOF, which may act as a protective variant downstream of TBX1, haploinsufficiency of which is responsible for congenital heart disease in individuals with 22q11DS.

Since the last survey, >10 years ago, chorionic villus sampling training has declined further. A decrease in the number of procedures that are performed is the leading barrier to this training.

No abstract

To evaluate the prefrontal space (PFS) ratio of fetuses of African descent without Down syndrome and compare it to the PFS ratio previously established in a homogeneous Caucasian population to determine whether there is a difference in the ratio in these two groups. The PFS ratio was calculated retrospectively from stored 2D images of 100 African, African-American and African-Caribbean fetuses in the second and third trimester performed at the authors' center. Other data including the maternal age, gestational age, and ethnicity were collected. An unpaired T test was used to compare the previously published Caucasian mean, 0.97 (SD 0.29) with the mean established for the black population 1.37 (SD 0.44). The difference between these two PFS ratios was found to be significant (p \ 0.0001). This pilot study suggests a significant difference in the PFS in the non-Caucasian population. In order to use the PFS as a sonographic screening tool for Down syndrome, it will be important to determine normal values in different ethnic populations.

We found a low fetal cardiac anomaly rate in studies performed for suboptimal views on obstetric ultrasound. The majority of women referred for this indication were obese. The practice of routine referral for this indication deserves further evaluation.

No abstract