Primary ovarian insufficiency with t(5;13): a case report and literature review on disrupted genes.

OBJECTIVES: To report a woman with primary ovarian insufficiency (POI) with reciprocal translocation between chromosomes 5 and 13. METHODS: Chromosomal analysis (G-banding) of a 39-year-old woman with elevated gonadotropin levels and secondary amenorrhea and review of the literature with a special focus on disrupted genes at the reported breakpoints. RESULTS: A reciprocal translocation between the long arms of chromosomes 5 and 13 was identified in the patient (46,XX,t(5;13)(q13;q14)). Investigation of the breakpoints revealed that the 13q14.1 region encompasses FOXO1 (forkhead box 1) gene, which has an important role in granulosa cell function and follicle maturation. CONCLUSIONS: Autosomal translocations are rare in women with POI. We have reported the first case of a de novo reciprocal translocation involving chromosomes 5 and 13 in a POI patient. As one of the breakpoints encompasses the FOXO1 gene, it seems that disruption of this gene can be the cause of POI in this patient. This provides further evidence on the role of autosomal translocations in disrupting POI-associated genes. Therefore, concentrating on the genes at the breakpoints will be helpful to delineate the new biological pathways or genes involved in POI pathogenesis.

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.

Mosaic supernumerary ring chromosome 19 identified by comparative genomic hybridisation.

We report the use of comparative genomic hybridisation (CGH) to define the origin of a supernumerary ring chromosome which conventional cytogenetic banding and fluorescence in situ hybridisation (FISH) methods had failed to identify. Targeted FISH using whole chromosome 19 library arm and site specific probes then confirmed the CGH results. This study shows the feasibility of using CGH for the identification of supernumerary marker chromosomes, even in fewer than 50% of cells, where no clinical or cytogenetic clues are present.

A new strategy for cryptic telomeric translocation screening in patients with idiopathic mental retardation.

Cryptic unbalanced chromosome rearrangements in the telomeric bands of human chromosomes constitute a significant cause of "idiopathic" mental retardation. Here, we have described a new strategy based upon comparative genomic hybridisation (CGH) to screen for these abnormalities. A modified CGH analysis showed three unbalanced cryptic rearrangements in five patients from three families. These chromosome abnormalities and their balanced forms in the relatives were then confirmed by fluorescence in situ hybridisation (FISH). This study describes a new approach to the diagnosis of cryptic translocations between the G band negative ends of chromosomes and confirms the significant contribution of cryptic telomeric rearrangements to idiopathic mental retardation.