Genetics in the Third Millennium
Volume:4 Issue: 4, 2007

Ataxia-telangiectasia is an autosomal recessive disorder affecting 1/40000 to 1/100000 of reported populations. There is 25% possibility for having an affected child when parents are carriers for ATM gene mutation. There is no cure available for this disease and prenatal testing is strongly recommended to prevent this disease. Although preferred method is the direct mutation analysis of ATM gene, but large size of the ATM gene with 63 exons and the large number of possible mutations in patients considerably limit efficiency of mutation analysis as a choice in diagnosis. Indirect method is a better tool when parents are not carriers of founder mutation and pass different mutations to their children. Indirect molecular diagnosis using ATM related molecular markers facilitates prenatal diagnosis of AT children. In this study, four molecular markers: D11S2179, D11S1787, D11S535, D11S1343 are genotypes in 12 unrelated families (19 patients) from different regions of IRAN. Those markers are amplified using extracted sequence primers from Gene Bank with their described PCR conditions. The amplified products were separated using denaturing PAGE gels, and the data were analyzed to detect their pattern of inheritance in each family. In all families, segregation of alleles were according to mandelian inheritance and affected chromosomes were distinguishable from unaffected ones. All carriers and affected patients were diagnosed accurately. Thus, this method is effectively usable in prenatal diagnosis of ataxia telangiectasia.

Apoptosis or programmed cell death is a process which occurs in the cell as a result of stress, damage, or crowding, or when the cell is no longer needed. During this process, the DNA is broken up and the entire cell is consumed by phagocytes around the body. Understanding of the apoptosis mechanism has provided a basis for novel targeted therapies that can induce death in cancer cells or sensitize them to established cytotoxic agents and radiation therapy. Regulation of apoptosis by molecules that effect functional proteins of apoptosis is one of the new ways for cancer therapy through inhibition of tumor growth. New research for cancer treatment by novel agents include those targeting the extrinsic pathway such as tumor necrosis factor-related apoptosis-inducing ligand receptor 1, and those targeting the intrinsic Bcl-2 family pathway such as Antimycin A (antisense bcl-2 oligonucleotide) have shown interesting results of some cancers inhibition and treatment. This review will discuss current knowledge about the pathways and new treatments that target them.

Signal transduction pathway was known as transmission process of molecular signals from extracellular surface to cytosol. A few signal transduction pathways are hyper- activated in cancer cells due to mutations in oncogenes and tumor suppressor genes that finally are led to block differentiation، excessive proliferation and apoptosis inhibition. In the last several years، there were major progress towards understanding of the molecular mechanisms of signal transduction pathways and cancer that have been led to design and development of drugs for cancer treatment by inhibiting these pathways. In contrast to chemotherapy and radiotherapy، signal transduction therapy was very selective and less toxic، and it’s to be hoped that early chemotherapy and radiotherapy would be removed by signal transduction therapy in cancer treatment.

The child is a 2½-year-old female. Parents are first cousins. She has skull bone defect, especially at the frontoparietal region, reduced lacrimation, alopecia and trichorhexis nodosa, and a dysmorphic face (depressed flat nasal bridge, hypertelorism and epicanthal folds). Mentality and developmental milestones are normal. To the best of our knowledge, this association is a new syndrome and has not been previously reported.

Lipid storage diseases are a group of metabolic disorders characterized by an enzyme defect leading to progressive accumulation of heterogeneous undigested lipid substance in the lysosomal organelles, causing variety of diseases according to defective gene and accumulated lipid in the different organ's cells.This study was based on enzymatic assays were performed for 409 affected members of two hundred and thirty-three families whom we had screened for metabolic disorders from August 1990 to November 2006. For ruling in/out of the suspected disorder, assay of urine, blood and skin fibroblasts were performed in Erasmus University. The necessary samples were taken according to the established protocols. Among the received 409 samples, 158 samples were suspected to have some forms of lipid storage diseases, 48 did not have the suspected enzyme defect and no diagnosis was established. In 84 cases, a diagnosis was reached with the first enzyme assay. In the remaining 25 cases, the first diagnosis which was metachromatic leukodystrophy in the majority of cases was negative and the second enzyme assay for another disorder after further workup proved to be positive and diagnostic. After enzyme assay 114 individuals were shown to have some lipid storage disorder.The highest number of cases studied is the Neimann-Pick cases with 22 members from 14 families, followed by 17 members from 16 families with Metachromatic leukodystrophy, 14 cases from 11 families referred for Gaucher and 10 families with 10 affected members with Tay Sachs. In our experience, emphasis on clinical workup prior to testing can cut down unnecessary expenses, time and effort.

Aarskog-Scott syndrome (ASS) is an X-linked disorder, characterized by facial, skeletal and genital anomalies. It is also known as faciogenital dysplasia (FGDY, OMIM No. 305400) and facio-digito-genital syndrome. The main features are short stature, hypertelorism, short hands and feet, and shawl scrotum. We are reporting 7 cases with this syndrome that were referred to our genetic center from 1995 to 2006 for clinical genetic counseling and cytogenetic study.