First-trimester screening for chromosomal abnormalities by integrated application of nuchal translucency, nasal bone, tricuspid regurgitation and ductus venosus flow combined with maternal serum free ß-hCG and PAPP-A: a 5-year prospective study.

OBJECTIVE: To investigate the performance of first-trimester screening for chromosomal abnormalities by integrated application of nuchal translucency thickness (NT), nasal bone (NB), tricuspid regurgitation (TR) and ductus venosus (DV) flow combined with maternal serum free ß-human chorionic gonadotropin (fß-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at a one-stop clinic for assessment of risk (OSCAR). METHODS: In total, 13,706 fetuses in 13,437 pregnancies were screened for chromosomal abnormalities during a period of 5 years. Maternal serum biochemical markers and maternal age were evaluated in combination with NT, NT + NB, NT + NB + TR, and NT + NB + TR + DV flow data in 8581, 242, 236 and 4647 fetuses, respectively. RESULTS: In total, 51 chromosomal abnormalities were identified in the study population, including 33 cases of trisomy 21, eight of trisomy 18, six of sex chromosome abnormality, one of triploidy and three of other unbalanced abnormalities. The detection rate and false-positive rate (FPR) for trisomy 21 were 93.8% and 4.84%, respectively, using biochemical markers and NT, and 100% and 3.4%, respectively, using biochemical markers, NT, NB, TR and DV flow. CONCLUSION: While risk assessment using combined biochemical markers and NT measurement has an acceptable screening performance, it can be improved by the integrated evaluation of secondary ultrasound markers of NB, TR and DV flow. This enhanced approach would decrease the FPR from 4.8 % to 3.4 %, leading to a lower number of unnecessary invasive diagnostic tests and subsequent complications, while maintaining the maximum level of detection rate. Pre- and post-test genetic counseling is of paramount importance in either approach.

A novel truncating mutation in the E-cadherin gene in the first Iranian family with hereditary diffuse gastric cancer.

AIMS: Hereditary Diffuse Gastric Cancer (HDGC) is a dominantly inherited familial cancer syndrome resulting from germline mutations of the E-cadherin (CDH1) gene. The first Iranian family with HDGC is herein reported. METHODS: The family fulfilled the International Gastric Cancer Linkage Consortium (IGCLC) criteria for HDGC. The entire coding region of the CDH1 gene was analysed by direct sequencing in an obligatory carrier. Subsequent molecular genetic tests were done on other at risk individuals to identify mutation carriers. RESULTS: A novel heterozygous 2275G>T mutation in exon 14 of the CDH1 gene was detected. This nonsense mutation generates a premature stop codon at position 758 giving rise to a truncated E-cadherin protein lacking cytoplasmic region. The specified mutation was detected in the index case and her asymptomatic son who underwent prophylactic gastrectomy. CONCLUSION: The first Iranian family with HDGC which carries a novel CDH1 germline mutation is reported.

Molecular cytogenetic analysis of urothelial carcinomas using urine samples.

Urinary cells obtained from voided urine specimens of 46 patients with urothelial carcinomas (UCs) and 10 normal individuals were analyzed with 3 different centromeric fluorescence in situ hybridization (FISH) probes. The overall sensitivity of cytology was 48.9% compared to 95.7%with the FISH technique. The minimum values were found for stage Ta and grade 1 (90.5 and 89.4) and sensitivity of FISH in other stages and grades was 100%. Chromosome 3 demonstrated the most frequent chromosomal abnormality in all samples (43%), followed by chromosome 17 (32%) and chromosome 7 (25%). There was a statistically significant association between the number of cell abnormalities in chromosome 17 and the tumour stage (p value=0.02). No relationship was found between the type of chromosomal abnormality and grade. Thus feasibility and reliability of a FISH based approach was confirmed for detection of UC in urine samples.