No abstract

Objective To evaluate the use of array comparative genomic hybridization (aCGH) for prenatal diagnosis, including assessment of variants of uncertain significance, and the ability to detect abnormalities not detected by karyotype, and vice versa. Methods Women undergoing amniocentesis or chorionic villus sampling (CVS) for karyotype were offered aCGH analysis using a targeted microarray. Parental samples were obtained concurrently to exclude maternal cell contamination and determine if copy number variants (CNVs) were de novo, or inherited prior to issuing a report. Results We analyzed 300 samples, most were amniotic fluid (82%) and CVS (17%). The most common indications were advanced maternal age (N = 123) and abnormal ultrasound findings (N = 84). We detected 58 CNVs (19.3%). Of these, 40 (13.3%) were interpreted as likely benign, 15 (5.0%) were of defined pathological significance, while 3 (1.0%) were of uncertain clinical significance. For seven (~2.3% or 1/43), aCGH contributed important new information. For two of these (1% or ~1/150), the abnormality would not have been detected without aCGH analysis. Conclusion Although aCGH-detected benign inherited variants in 13.3% of cases, these did not present major counseling difficulties, and the procedure is an improved diagnostic tool for prenatal detection of chromosomal abnormalities.

No abstract

Amniotic fluid samples were obtained from 10 pregnant women undergoing routine amniocentesis procedure. Approximately 45 min prior to the procedure, five of the women ingested placebo capsules, whereas the remaining five ingested capsules containing the essential oil of garlic. Randomly selected pairs of samples, one from a woman who ingested garlic and the other from a woman who ingested placebo capsules, were then evaluated by a sensory panel of adults. The odor of the amniotic fluid obtained from four of the five women who had ingested the garlic capsules was judged to be stronger or more like garlic than the paired samples collected from the women consuming placebo capsules. Thus, garlic ingestion by pregnant women significantly alters the odor of their amniotic fluid.

Background Congenital diaphragmatic hernia (CDH) is a life-threatening birth defect. Most of the genetic factors that contribute to the development of CDH remain unidentified. Objective Identify genomic alterations that contribute to the development of diaphragmatic defects. Methods A cohort of 45 unrelated patients with CDH or diaphragmatic eventrations were screened for genomic alterations by array comparative genomic hybridization (aCGH) or SNP-based copy number analysis. Results Genomic alterations that were likely to have contributed to the development of CDH were identified in eight patients. Inherited deletions of ZFPM2 were identified in two patients with isolated diaphragmatic defects and a large de novo 8q deletion overlapping the same gene was found in a patient with non-isolated CDH. A de novo microdeletion of chromosome 1q41q42 and two de novo microdeletions on chromosome 16p11.2 were identified in patients with non-isolated CDH. Duplications of distal 11q and proximal 13q were found in a patient with non-isolated CDH and a de novo single gene deletion of FZD2 was also identified in a patient with a partial pentalogy of Cantrell phenotype. Conclusions Haploinsufficiency of ZFPM2 can cause dominantly inherited isolated diaphragmatic defects with incomplete penetrance. Our data define a new minimal deleted region for CDH on 1q41q42, provide evidence for the existence of CDH-related genes on chromosomes 16p11.2, 11q23-24 and 13q12 and suggest a possible role for FZD2 and Wnt signaling in pentalogy of Cantrell phenotypes. These results demonstrate the clinical utility of screening for genomic alterations in individuals with both isolated and non-isolated diaphragmatic defects.

No abstract

No abstract

No abstract