Developments in Genetics: Better Management of Ovarian Cancer Patients.

The purpose of this article is to highlight the new advancements in molecular and diagnostic genetic testing and to properly classify all ovarian cancers. In this article, we address statistics, histopathological classification, molecular pathways implicated in ovarian cancer, genetic screening panels, details about the genes, and also candidate genes. We hope to bring new information to the medical field so as to better prevent and diagnose ovarian cancer.

Genotype-phenotype correlations in a mountain population community with high prevalence of Wilson's disease: genetic and clinical homogeneity.

Wilson's disease is an autosomal recessive disorder caused by more than 500 mutations in ATP7B gene presenting considerably clinical manifestations heterogeneity even in patients with a particular mutation. Previous findings suggested a potential role of additional genetic modifiers and environment factors on phenotypic expression among the affected patients. We conducted clinical and genetic investigations to perform genotype-phenotype correlation in two large families living in a socio-culturally isolated community with the highest prevalence of Wilson's disease ever reported of 1 ∶ 1130. Sequencing of ATP7B gene in seven affected individuals and 43 family members identified a common compound heterozygous genotype, H1069Q/M769H-fs, in five symptomatic and two asymptomatic patients and detected the presence of two out of seven identified single nucleotide polymorphisms in all affected patients. Symptomatic patients had similar clinical phenotype and age at onset (18 ± 1 years) showing dysarthria and dysphagia as common clinical features at the time of diagnosis. Moreover, all symptomatic patients presented Kayser-Fleischer rings and lack of dystonia accompanied by unfavourable clinical outcomes. Our findings add value for understanding of genotype-phenotype correlations in Wilson's disease based on a multifamily study in an isolated population with high extent of genetic and environmental homogeneity as opposed to majority of reports. We observed an equal influence of presumed other genetic modifiers and environmental factors on clinical presentation and age at onset of Wilson's disease in patients with a particular genotype. These data provide valuable inferences that could be applied for predicting clinical management in asymptomatic patients in such communities.

The importance of screening and prenatal diagnosis in the identification of the numerical chromosomal abnormalities.

BACKGROUND AND AIMS: The obstetric care of a pregnancy, as it is practiced today, includes non-invasive screening approaches as well as invasive procedures for the definitive prenatal diagnosis of fetal disorders correlations between indications for prenatal cytogenetic diagnosis and results of the chromosomal analysis made upon fetal cells. The aim of our study was to evaluate the correlations between the screening test results and results of chromosomal analysis on fetal cells. METHODS: Amniotic fluid samples from 1159 pregnant women were studied with the rapid FISH method and the cytogenetic analysis (karyotype). The results from both methods were compared. RESULTS: The indications to perform prenatal cytogenetic diagnosis for numerical chromosomal abnormalities were: abnormal results of double or triple test, advanced maternal age, fetal abnormality detected through ultrasound examination, and positive family history for chromosomal anomalies. In our study we identified 30 cases with abnormal numeric chromosomes (18 cases of trisomy 21, 4 cases of trisomy 18, 3 cases of trisomy X, 1 case of monosomy, 2 cases of trisomy XYY, 1 case of trisomy XXY and 1 case of triploidy). CONCLUSIONS: This report confirms the importance of screening and the cytogenetic diagnosis in the identification of the numerical chromosomal abnormalities.

Methylenetetrahydrofolate dehydrogenase (MTHFD) enzyme polymorphism as a maternal risk factor for trisomy 21: a clinical study.

Recent reports linking Down syndrome (DS) to maternal polymorphism at the methylenetetrahydrofolate dehydrogenase (MTHFD) locus have generated a great interest among investigators in the field. In the current study, we examine one genetic polymorphism involved in homocysteine/folate pathway as a risk factor for DS in a Romanian urban-area women cohort. Our results show that the frequencies of MTHFD1 alleles, as well as the frequencies of MTHFD11958 genotypes (GG, GA, AA, GA+AA) do not correlate with DS pregnancies, demonstrating no difference between the case and control groups, as opposed to the findings of Scala et al. (2006) on an Italian cohort.

RFC - 1 Gene Polymorphism and the Risk of Down Syndrome in Romanian Population.

BACKGROUND AND AIMS: There is evidence that the polymorphisms of the genes involved in folate metabolism may be associated with higher risk of Down syndrome (DS) pregnancy. The aim of the present study was to investigate the effect of A80G polymorphism in reduced folate carrier 1 (RFC1) gene on the maternal risk for DS. METHODS: In our study, twenty-two DS mothers and forty-two mothers who had no children with DS were evaluated. Genomic DNA was isolated from whole peripheral blood collected on EDTA, using peqGOLD blood DNA mini kit (ATP Biotech) following the manufacturer's instructions. RESULTS: The results show that the frequencies of RFC1 alleles, as well as the frequencies of RFC1 A80G genotypes (GG, GA, AA, GA+AA) do not correlate with DS pregnancies, demonstrating no difference between the case and control groups. CONCLUSIONS: In the present study, we did not find any statistically significant association between RFC-1 polymorphic genotype and history of DS pregnancies; thus, the relationship between RFC-1 polymorphism and DS appears to be only a supposition and the next step in our study is the catamnestic evaluation of our patients with DS babies for two years.