Genetics in the Third Millennium
Volume:6 Issue: 1, 2008

Severe combined immunodeficiency (SCID) is a rare and mortal disorder with X-linked and autosomal recessive inheritance. Many genes is related to the disease including ADA, RAG1, RAG2, Artemis, CD45, JAK3, IL7R which have different clinical presentation and T and B lymphocytes profile. In this study, we investigated gene mutations in suspected patients referred to the Children Medical Center Hospital, Department of Allergy & Clinical Immunology. Blood tests for patients showed T-B- profile, so we selected the genes that were responsible in T and B cell maturation (ADA, RAG1 and RAG2). According to our possibilities, we studied ADA and RAG1 genes in patients. We did the test by PCR and Sequencing method. Also total ADA activity (tADA) and its isoenzymes (ADA1 and ADA2) were estimated in patients. Our investigation showed two mutations in ADA gene and three in RAG1 gene. In this study, we offer a new protocol for investigation of RAG1 gene. This is the first study on diagnosis of SCID patients through genetic investigation in Iranian patients.

Myotonic Dystrophy type I (DM1) the most common form of muscular dystrophy in adults affecting 1/800 individuals is a dominantly inherited disorder with a multi-systemic pattern affecting skeletal muscle, heart, eye, endocrine and central nervous system. DM1 is associated with the expansion and instability of a trinucleotide (CTG) repeat in the 3 untranslated region of the myotonic dystrophy protein kinase (DMPK) gene located on choromosome 19q13.3. The normal copy number is 5-37 CTG repeat whereas it is expanded in DM1 patients and the expansion size broadly correlates with the severity of the symptoms. The aim of this study was to determine the clinical and genetic characteristic of DM1 in Iranian patients for genotype-phenotype correlation methods. Clinical assessment was based on the muscular disability rating scale (MDRS) and a sum of symptoms score (SSS). Molecular analysis (PCR & Southern blot) was used to clarify uncertain clinical diagnoses and confirm the clinical findings. Forty six patients from twenty five DM1 families were reviewed. In all the DM1 patients, the wide clinical symptoms confirmed the reported phenotypic vaiability of disorder. The range of CTG expansion of the mutated allele was 97-833 CTG repeats and an inverse correlation between age of onest and repeat length was observed. A clear relation between the size of the CTG repeat and the clinical disease score (MDRS) was found but not with SSS. No correlation was seen between the endocrine dysfunction and the expansion size in DM1 patients.

Because of efficient progress in controlling common and lethal environmental, infectious and nutritional disorders, gradually referral for genetic and metabolic disorders are being more common. Currently about 20 to 30% of referral and academic hospital beds are occupied by these patients. Also, about 20% of mortality of patients in the early pediatric age group belongs to these disorders. More than 100 years ago for the first time, Sir Archibald Garrod introduced some metabolic disorders. More than 500 different phenotypes of metabolic disorders identified and categorized in the literature. There are a huge number of very different metabolic pathways inside the cells. In a metabolic pathway, a biochemical molecule in a step by step reaction synthesized or degraded and changed to the new one. If the responsible enzyme was deficient in a specific reaction, a block in that pathway will occur. The end result would be accumulation of the enzyme’s substrate or deficiency of its product. Both of them can cause apoptosis or cell death and a specific disabling or serious phenotype. In this article I will try to explain some of the clinical and pathophysiologic characteristics and classification of these rare disorders briefly. Also I will explain available modern technologies that are used for evaluation, diagnosis, treatment, prevention, and screening. I believe that by considering the mentioned issues, we will be able to approach better and more logically confronting these patients. For some of these disorders specific treatment is available. For those that there is no therapy, reaching an accurate diagnosis will help us to offer necessary information in genetic counseling sessions, and prevent the recurrence of the tragedic problem in the next pregnancies.

The stem cell possesses two distinct traits: self-renewal and differentiation capacity. The stem cell population is comprised of two main cell types: embryonic stem cells and adult stem cells. Researches on the stem cells provoked ways to utilize their potential for therapeutic treatments of multiple neurological disorders. There are three different approaches in neural repair with the usage of stem cells: cell replacements, neuroprotection and gene delivery which are highly developed in treating neurological disorders such as Parkinson and multiple sclerosis but these approaches have their own problems. In comparison with embryonic stem cells, adult stem cells have more application in neural repair, because the usage of embryonic stem cells raises ethical issues, and will involve allograft transplantation and are of much risk for tumor formation. Taking all of this into account, utilizing adult stem cells are in priority. Furthermore, injection of molecules such as bFGF and EGF leads to induction of neurogenesis that can be helpful in neural repair.

Epidermolysis bullosa (EB) is a group of genetic conditions that cause the skin to be very fragile and to blister easily. Epidermolysis bullosa simplex (EBS) is one of the major forms of the disease. The signs and symptoms of this condition vary widely among affected individuals. Blistering may primarily affect the hands and feet in mild cases. In such cases, blisters usually heal without leaving scars. Severe cases of the disease involve widespread blistering that can lead to infections, dehydration and other medical problem. Researchers have identified four major types of epidermolysis bullosa simplex. They are caused by mutations in the same genes. Four type of EBS includes EBS-WC, EBS-K, EBS-MP and EBS-DM. The mildest form of EBS is EBS-WC. Mutation in the KRT14 and KRT5 genes are responsible for the four major types of EBS. These genes provide instructions for making protein called Keratin 5 and Keratin 14. These tough, fibrous protein works together to provide strength and resiliency to the outer layer of the skin. Mutations in either the KRT14 or KRT5 genes cause cells in the epiderm to become fragile and easily damaged. In this article, we will acquaint with this disease and the clinical diagnosis of each subtype.

Blood groups are inherited genetically but environment can influence on their durability. transformation and till now many studies have been performed about relation of blood groups with different diseases like various cancers, gastric ulcers, cardiovascular disease and high blood cholesterol. The knowledge of blood type as a risk factor for cancer and other diseases is one of the important tools that can be beneficial for preventing of these diseases in the future. Although it must be considered that for determinating of predisposition to various diseases blood type must be considered with other risk factors. And having a special blood type is not a definitive cause for predisposing to a particular disease and vice versa. In this study we will aquinted with the relation of major relationship of some cancers with blood groups.

Neonatal diabetes divided into transient and permanent forms. Pancreatic agenesis is a very rare cause of permanent neonatal diabetes. In this paper, two male patients with neonatal hyperglycemia are reported. They were very sensitive to insulin and malabsorption syndrome gradually appeared in them. The first patient had hyperglycemia on the third day of life and steatorrhea, edema and anemia appeared during first two months. The second one was brought at 10 days of life but her mother had noted to fatty and frequent stools. Anemia and edema appeared during admission. Sonography in the first patient reported normal pancreas and caused delay in diagnosis, but CT-scan was useful for correct diagnosis in the second patient. Hyperglycemia accompanied by insulin sensitivity, malabsorption signs and symptoms, lack of anomalies and low birth weight should be assumed as pancreas agenesis and CT-scan is useful way for diagnosis.

Cardiofaciocutaneous (CFC) syndrome is a rare genetic disorder. It characterized by a distinctive facial appearance, cardiac and cutaneous abnormalities and mental retardation. The heart defects include pulmonic stenosis, septal defect, hypertrophic cardiomyopathy and rhythm disturbances. Ectodermal abnormalities include sparse, friable and curly hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. We are reporting a 5-year-old boy with mental retardation, bitemporal narrowing, down slanting palpebral fissure, depressed nasal bridge, coarse face, sparse and brittle hair, high frontal hairline, hypohidrotic and dry skin, atopic dermatitis. We believe that our patient is a case of cardiofaciocutaneous syndrome.