Genetics in the Third Millennium
Volume:7 Issue: 1, 2009

With significant improve in health-care and treatment of infectious diseases, genetic disorders have created a new era of notification. Changes in social attitude towards family life and tendency of parents for limited number of children, sense of responsibility of parents for mental and physical healthiness of children along with their education, needed a new strategy. Since most genetic disorders did not have definitive treatments, physicians tried to prevent these disorders and their disabilities. Early diagnosis of these diseases started in 1934, and first prenatal diagnosis (amniocentesis) was reported in 1967. Rapid progress in cytogenetic and molecular genetic, necessitates each major medical center to have a "prenatal diagnosis department". The first amniocentesis in Iran was done in 1988 with a delay of 20 years. Different problems including no permission for abortion, lack of public knowledge especially authorities and physicians about provided services, and financial limitations of families to afford the expenses of laboratory tests, all were major obstacles to use this technology. Gradually, most of these problems have been solved, and nowadays many centers throughout the country provide these services. In this article, a short list of 15,600 prenatal diagnoses (amniocentesis, chorionic villus sampling, etc) including 13,225 chromosomal abnormalities, 1786 hemoglobinopathies, 283 myopathies, 197 metabolic disorders, 171 triple nucleotide repeats, 32 rare diseases, and eight dermatologic diseases are presented. From 6,473 performed amniocenteses (from 21 February 2007 to 11 April 2009) for evaluation of chromosomal abnormalities, 230 (3.6%) chromosomal abnormalities and 12 (0.2%) unsuccessful responses were documented. In other cases, except for a very few ones who ended in spontaneous abortion, pregnant women continued their pregnancy. Samplings of the amniotic fluid and the placenta were derived by experienced specialties with a very few complications (0.2%), and misdiagnosis was nearly zero.

Larsen syndrome (LS) is one of the rare autosomal dominant chondrodystrophias, characterized by multiple dislocations of the large joints, midfacial hypoplasia, and cleft palate. Recently it has been known that some missense mutations or small in-frame deletions in the gene Filamin B (FLNB) may cause autosomal dominant Larsen syndrome. Filamin B gene encodes a very important cytoskeletal protein named filamin B. This protein has central role on development of inter-cellular connective tissue, joint cartilage, and vertebral segmentation and development. In this article, we report a large Iranian pedigree including about 30 affected individuals to autosomal dominant Larsen syndrome in four subsequent generations. After ascertaining Larsen syndrome by clinical and radiological studies, in some of the available individuals of different branches of the pedigree, molecular analysis by dHPLC, direct sequencing, and endonuclease digestion methods have been carried out to detect responsible mutations in filamin B gene. We detected a point mutation on nucleotide 679 (679G>A) leading to substitution of glutamic acid instead of lysine in amino acid number 227 (E227K). The mutation is one of the recurrent missense mutations that have been reported before in several families. In this pedigree, we found variable phenotypes according to the severity and spectrum of the symptoms.

There are three kinds of RNA, all apparently involved in making protein: ribosomal RNA (rRNA), transfer RNA (tRNA) and everything else, which was assumed to be mRNA. Recently, many other RNAs have been isolated biochemically and several different systematic screens have identified a surprisingly large number of non-coding RNA (ncRNA) genes that produce functional RNA molecules rather than encoding proteins. ncRNAs, as with protein-coding genes, are a heterogeneous group and have been divided into three different classes according to their length and their function. A variety of complex mechanisms such as gene silencing, gene transcription, DNA demethylation, RNA interference and others have already been connected to their function. Also, the increasing data linking ncRNAs to different processes provides proof that they are more important than previously thought. Key words: Non-coding RNA (ncRNA) RNA interference (RNAi) MicroRNA (miRNA) Small interfering RNA (siRNA) Gene silencing.

Nanotechnology is on of the growing branches of science that involves the production, manipulation and use of materials ranging in size from less than a micron. Although nanomaterials may be synthesized using chemical systems, but on interesting way for scientists is the production of such materials by living organisms particularly microorganisms and biological processes in the synthesis of nanoparticles. In this review, we reviewed on the rule of microorganisms and plants in the synthesis of nanoparticles and also different usages of these materials.

Telomeres are the non-coding portions of DNA sequences at the end of each linear chromosome. Mammalian telomeres consist of 5-8 nucleotides with repeated sequences of TTAAGGG. Their functions are identifying the end of chromosomes, preventing the end of chromosome to be adhesive, protecting the chromosome termini from incorrect connection and degradation, appropriate chromosome location in a nucleus, and synthesize of the end of chromosomes in DNA replication. In DNA replication procedures, lagging strand synthesis are observed unable to copy the extreme end of linear chromosomes. This results in shortening of the length of DNA molecules in several mitosis, which is called “end replication problem”. In most eukaryotic cells, telomerase, which is a ribonucleoprotein DNA polymerase complex, as a reverse transcriptase solve the problem by telomere synthesis. In the absence of telomerase activity, telomeres progressively are become short and potentially deleted genes. Due to this shortness and lack of information, the cell is driven to death so the level of telomerase activity is an important factor in determining telomere length and in lifespan and reproductive capacity of cells. Tumor cells have a special capability in producing telomerase, so this matter could be regarded as a mean in treating cancers.

Telomeres are conserved sequences at the end of human sticky chromosomes that serve as reservoir of chromosomes end destruction. Telomerase, a ribonucleoprotein complex, is a key regulator of telomere length maintenance in stem cells. Enzymatic activity of telomerase is obviously reported in multiple human cancer cells, whereas no activity is detected in adjacent normal cells. This selectivity of function of telomerase and its specificity to cancer cells, bring the thought of cancer therapy via telomerase inhibition. Specifically blocking of telomerase subunits, catalytic protein and template RNA, with high sensitivity is helpful in molecular drug invention. These drugs are low toxic due to their specific action and act synergistically to cure cancer dramatically. In this report we present the new progression in this filed with benefits and complication of each of them.

Cystic fibrosis (CF) is the most common autosomal recessive disease in western countries. This disease is caused by mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene. This gene is located on the long arm of chromosome 7 and encompasses 250 Kb. CFTR expressed in the apical membrane of exocrine epithelial cells functions as a chloride channel and its activity is regulated by cAMP. Over 1400 mutations have been reported in CFTR gene. Frequency of these mutations is interestingly different in various populations. The most common mutation is a deletion of phenylalanine at position 508 (ΔF508) in most countries. So far, the studies on Iranian patients have shown that the frequency of ΔF508 is more than other mutations, but it is less than western countries. It seems heterogeneity of mutations is high in Iranian patients and most patients are compound heterozygote. Our studies on CF patients sequenced all exons of CFTR gene show that most Iranian patients are compound heterozygote carrying a severe and a mild mutation or two mild mutations. So Iranian CF phenotype is milder than patients in western countries. Sequencing is the best technique for diagnosis of CF patients in Iran. In this article, we will be familiar with this disease and its consequence in Iran

Childhood disintegrative disorder (CDD) is one of the least common entities in autistic spectrum. The disorder characterized by clinically significant loss of previously acquired skills, before age 10 years, in a child with apparently normal development for at least the first 2 years after birth. Comorbidity of Down syndrome and autistic disorder is known, however occurrence of childhood disintegrative disorder in Down syndrome is scantly reported. We report a 7 years old boy with Down syndrome, whose acquired skills, such as speech ability and social interactions, were lost during a three months period.

Townes-Brocks syndrome (TBS) is characterized by imperforated anus (82%), dysplastic ears (88%) (over-folded superior helices and preauricular tags) and frequently associated with sensorineural and/or conductive hearing impairment (65%), and thumb malformations (89%) (triphalangeal thumbs, duplication of the thumb, preaxial polydactyly and rarely hypoplasia of the thumb). Renal impairment (27%), including end-stage renal disease (ESRD) (42%), may occur with or without structural abnormalities (mild malrotation, ectopia, horseshoe kidney, renal hypoplasia, polycystic kidneys, vesicoutereral reflux). Congenital heart disease occurs in 25%, genitourinary malformations (36%). Mental retardation occurs in approximately 10% of cases. It is autosomal dominant disease with variability in the severity of expression. We are reporting a 8-year-old girl with dysplastic ears, deafness, dysplastic thumbs, small kidneys, history of repaired imperforated anus, and rectovaginal fistula. She is also diagnosed with congenital adrenal hyperplasia. We believe our patient is the first case of Townes-Brocks syndrome with congenital adrenal hyperplasia.