Methods ASCERTAINMENTSixty-four patients with the diagnosis of RTS were ascertained through the Rubinstein-Taybi Parent Group (47 (73%)) and referrals from other genetic centres (17 (27%)). Clinical data, photographs, and medical records were collected on each patient to confirm the diagnosis of RTS. Thirty-nine specific traits, including growth parameters, were assessed for each patient. Since RTS is a short stature syndrome, microcephaly in this context was used as 1 SD below the 50th centile height age to assess true microcephaly in relation to body size and not small head size resulting from overall growth deficiency. Clinical assessment was made before knowledge of deletion status to minimise potential bias and to test the hypothesis that there are clinically distinguishable differences between deletion and non-deletion patients. CYTOGENETIC STUDIESPeripheral lymphocytes were cultured for 72 hours using conventional methods. Karyotyping with GTG banding was performed at the 550 to 750 band level. A minimum offive metaphase preparations were examined from each patient. MOLECULAR STUDIESThe RT1 cosmid (D16S237), approximately 56 kb in size, was obtained in an E coli MC 1046 host. The presence of the probe was confirmed by digestion with EcoRI, which yielded a specific 5.2 kb fragment. The cosmid was

No abstract

No abstract

Purpose Of 86,902 prenatal genome-wide cell-free DNA (cfDNA) screening tests, 4,121 were positive for a chromosome abnormality. This study examines 490 cases screen-positive for one or more subchromosomal copy-number variants (CNV) from genome-wide cfDNA screening. Methods Cases positive for one or more subchromosomal CNV from genome-wide cfDNA screening and diagnostic outcomes were compiled. Diagnostic testing trends were analyzed, positive predictive values (PPVs) were calculated, and the type of chromosomal abnormalities ultimately confirmed by diagnostic testing were described. Results CNVs were identified in 0.56% of screened specimens. Of the 490 cases screen-positive for one or more CNV, diagnostic outcomes were available for 244 cases (50%). The overall PPV among the cases with diagnostic outcomes was 74.2% (95% CI: 68.1–79.5%) and 71.8% (95% CI: 65.5–77.4%) for “fetal-only” events. Overall, isolated CNVs showed a lower PPV of 61.0% (95% CI: 52.5–68.8%) compared to complex CNVs at 93.9% (95% CI: 86.6–97.5%). Isolated deletions/duplications and unbalanced structural rearrangements were the most common diagnostic outcomes when isolated and complex CNVs were identified by cfDNA screening, respectively. Conclusion Genome-wide cfDNA screening identifies chromosomal abnormalities beyond the scope of traditional cfDNA screening, and the overall PPV associated with subchromosomal CNVs in cases with diagnostic outcomes was >70%.

Objective: To examine the relationship between the fraction of cell-free DNA (cfDNA) affected by aneuploidy compared to the overall fetal fraction of a prenatal screening specimen and its effect on positive predictive value (PPV). Method: CfDNA specimens positive for trisomy 13, 18, and 21 with diagnostic outcomes were analysed over a 22-month period in one clinical laboratory. For each positive specimen, a "mosaicism ratio" (MR) was calculated by dividing the fraction of cfDNA affected by aneuploidy by the overall fetal fraction of the specimen. PPVs were calculated and analyzed based on various MR ranges. Results: Trisomy 13 was the aneuploidy most commonly seen in mosaic form, followed by trisomy 18 and trisomy 21. Significant differences in positive predictive values were noted for all three trisomies between samples with an MR in the "mosaic" versus "non-mosaic" range, as well as between results classified as "lowmosaic" versus "high-mosaic." Conclusion: PPVs may be influenced, in part, by the mosaicism ratio associated with a particular result. The data generated from this study may be useful in providing more personalized risk assessments for patients with positive cfDNA screening results.