Testing For Gene Variants Research Articles

Prenatal Testing for Variants in Genes Associated with Hereditary Cancer Risk: Laboratory Experience and Considerations

Prenatal molecular genetic testing for familial variants that cause inherited disorders has been performed for decades and is accepted as standard of care. However, the spectrum of genes considered for prenatal testing is expanding due to genetic testing for hereditary cancer risk (HCR) and inclusion of conditions with associated cancer risk in carrier screening panels. A few of these disorders, such as ataxia telangiectasia and Bloom syndrome, include increased cancer risk as part of the phenotype, already meet professional guidelines for prenatal testing, and may be associated with increased cancer risk in heterozygous carriers. Additionally, recent studies implicate heterozygosity for variants in lysosomal storage disease (LSD) genes in HCR etiology. Currently, there is no specific professional guidance regarding prenatal testing for HCR. In order to determine the prevalence of such testing we reviewed 1345 consecutive prenatal specimens received in our laboratory for familial variant specific testing and identified 65 (4.8%) with a known or likely HCR component, plus 210 (15.6%) for LSD. These specimens were classified into five distinct categories for clarity and to enable evaluation. Our experience assessing prenatal specimens for variants associated with HCR, with or without a constitutional phenotype, provides metrics for and contributes to the points to consider in prenatal testing for HCR.

Phenotypic features of ciliary dyskinesia among patients with congenital cardiovascular malformations.

Cilia are cell membrane-bound organelles responsible for airway mucus clearance, establishment of left-right organ asymmetry, cardiogenesis, and many other functions in utero. Phenotypic features suggestive of respiratory ciliary dyskinesia among patients with heterotaxy syndrome, defined as complex cardiovascular malformations (CVM) and situs ambiguus (SA), has not been adequately explored. We hypothesized that there is a greater incidence of phenotypic features consistent with ciliary dyskinesia among patients with heterotaxy syndrome compared to patients with other CVM and laterality defects without heterotaxy syndrome. Thirty six subjects were identified by medical record search and divided into four groups based on situs status and type of CVM as follows: SA and complex CVM (group 1); SA and simple CVM (group 2); situs solitus and complex CVM (group 3); and situs solitus and simple CVM (group 4). Phenotype was assessed with a clinical questionnaire, nasal nitric oxide (NO) level, and pulmonary function testing. Those with complex CVM underwent additional testing for variants in genes involved in ciliary structure and function. The mean nasal NO level was significantly lower among all subjects with complex CVM regardless of situs anomalies (groups 1 and 3). There was no significant difference in respiratory symptoms or lung function among the four groups. No bi-allelic genetic mutations were detected among patients with complex CVM. This study identified a relatively lower mean nasal NO level, suggestive of relative ciliary dyskinesia, among subjects with complex CVM. Pulmonary function and clinical symptoms did not reflect significant pulmonary disease among those with complex CVM.

Molecular Genetic Markers as a Basis for Personalized Medicine / MOLEKULARNO-GENETIČKI MARKERI KAO OSNOV ZA PERSONALIZOVANU MEDICINU

Summary Nowadays, genetics and genomics are fully integrated into medical practice. Personalized medicine, also called genome-based medicine, uses the knowledge of the genetic basis of disease to individualize treatment for each patient. A number of genetic variants, molecular genetic markers, are already in use in medical practice for the diagnosis, prognosis and follow-up of diseases (monogenic hereditary disorders, fusion genes and rearrangements in pediatric and adult leukemia) and presymptomatic risk assessment (BRCA 1/2 for breast cancer). Additionally, the application of pharmacogenomics in clinical practice has significantly contributed to the individualization of therapy in accordance with the patient’s genotype and gene expression profile. Genetic testing for several pharmacogenomic markers (TPMT, UGT1A1, CYP2C9, VKORC1) is mandatory or recommended prior to the initiation of therapy. The most important achievement of genome-based medicine is molecular-targeted therapy, tailored to the genetic profile of a disease. Testing for gene variants in cancer (BCR-ABL, PML/RARa, RAS, BCL-2) is part of the recommended evaluation for different cancers, in order to achieve better management of the disease. The ultimate goal of medical science is to develop gene therapy which will fight or prevent a disease by targeting the disease causing genetic defect. Gene therapy technology is rapidly developing, and has already been used with success. Although medicine has always been essentially »personal« to each patient, personalized medicine today uses modern technology and knowledge in the field of molecular genetics and genomics, enabling a level of personalization which leads to significant improvement in health care.

Gene Testing Could Help Predict Drug Responses

Gene Testing Could Help Predict Drug Responses