Genetics in the Third Millennium
Volume:8 Issue: 2, 2010

Colorectal cancer (CRC) is the most gastrointestinal cancer in United States and Europe. It is the third most common cancer in Iranian men, and fourth in Iranian women. Codons 12 and 13 are the hot spots for mutations in colorectal cancer patients, which encodes the activated RAS protein. According to recent researches, somatic mutations in codons 12, 13 (exon1) of K-ras gene are discovered in 20% - 50% human CRCs. The aim of this study was to estimate the contribution of K-ras gene mutations in codons 12, 13 in the incidence, and its association with clinicopathologic information like age, sex, familial history, site of primary and histology in Iranian colorectal cancer patients. In this study, we have analyzed 59 tissue specimens of colorectal cancer patients using PCR/sequencing method for codons 12, 13 of K-ras gene. 20.3% of patients (10 in codon 12 and 2 in codon 13) have shown a point mutation. About 60% of mutations occur in rectum and 41.7% in colon. More than 80% of mutations were in adenocarcinomas and less mutations in mucinous. Most mutations were found over the age of 60. Only two patients (16.6%) had a familial history for cancer. According to low rates of k-ras mutations in codons 12, 13, we can say they are not common in Iranian patients. The mutation pattern for Iranian patients differs from other nationalities. Perhaps we can find point mutations in other exons, and we suggest whole genome sequencing for our patients.

Twenty one FISH tests for confirmation of Williams Beuren Syndrome (19 Peripheral blood, and two amniotic cells cultures) have been performed. FISH tests in four couples with one affected child of Williams Syndrome are negative for abnormal critical segment of del (7p11-23), which indicates that the deletion in the affected children is of de novo origin. There are two negative FISH tests out of 8 candidates suspected for WS. One is positive for Prader-Willi Syndrome, the other one is negative for WS, so far. One negative FISH test out of 8 indicates the importance of FISH test in detection of microdeletion disease, especially in Williams Beuren Syndrome.

Friedreich ataxia (FA) is an autosomal recessive disorder that caused by the expansion of GAA trinucleotide repeat in the first intron of gene X25 (1). FA is characterized by progressive ataxia and deep tendon areflexia in the lower limbs, dysarthria, skeletal deformities, Cardiomyopathy, muscle weakness and diabetes mellitus may be also found. Cardiomyopathy occurs in almost patients with FA (2). Cardiomyopathy is the most cause of death in FA patients (3). Aim of present study was to evaluate the size of GAA repeat and it′s correlation with age at onset and cardiomyopathy in these patients. Long PCR testing subsequently confirmed the diagnosing of FA and by identification of GAA repeat, an inverse correlation between size of repeat and age at onset and cardiomyopathy was found.

Serial analysis of gene expression or SAGE is a powerful technique that can be used for global analysis of gene expression. The result of a SAGE experiment is reported as a SAGE library, which contains the counts of various short segments (tags) of the cDNA clones. Unlike many other techniques SAGE does not require prior knowledge of the genes of interest and provides qualitative and quantitative data of every transcribed sequence in a particular cell or tissue type. The SAGE method is based on the isolation of unique sequence tags from individual mRNAs and serial concatenation of tags into long DNA molecules for lump-sum sequencing. SAGE has been widely applied to analyzing gene expression in many biological and medical studies. Some variations of the original SAGE were derived to improve the utility of SAGE in certain conditions for example microSAGE, miniSAGE, longSAGE, superSAGE, etc. In this review, we present an outline of the original method, the basic principle of SAGE, compare SAGE with microarray, some of the modified SAGE, discusses the advantages and limitations of SAGE as well as examples of applications.

Transendothelial migration of leukocytes (diapedesis), have vital role in both the innate and adaptive immune responses.This process consists of overlapping steps, including: activation of leukocytes, formation of weak adhesions, and translocation along the endothelium followed by stronger adhesions resulting in transmigration of leukocytes. Although the surface molecules used by leukocytes and endothelial cells during diapedesis have been well characterized, the mechanisms by which they regulate this process is poorly understood. In this minireview we introduce some of the involved molecules and mechanisms that play roles in this process.

Tay-Sachs disease is a rare autosomal recessive disorder of sphingolipid metabolism, caused by deficiency of enzyme ß hexosaminidase A, that leads to accumulation of GM2 ganglioside in cellular lysosomes. Clinical findings are progressive weakness, gradual loss of aquired neuromotor skills, and deterioration of intelligence from about 3 to 6 months of age, as well as seizure attacks and blindness. There is also evidence on progressive neurodegeneration. In most of the patients bilateral cherry red spot were reported on funduscopy. In this report, we present two patients with Tay-Sachs disease, which are confirmed by enzyme assay. In both of them ß hexosaminidase A activity were strongly decreased.

Larsen syndrome is a rare disease with autosomal dominant inheritance, although both autosomal dominant and recessive inheritance has been reported. It is characterized by multiple joint dislocation, peculiar face, and vertebral anomalies. We are reporting a one-year-old boy with hips and knees dislocation, talipes equinovarus, hypertelorism, depressed nasal bridge, prominent forehead. We believe that our patient is a new case of Larsen syndrome.

Severe overgrowth and tallness is very rare in human beings. The most common cause is gigantism due to the excessive secretion of the growth hormone، especially، before the closure of long bones’ epiphyseal growth plates. There are other rare disorders that are categorized on overgrowth syndromes. Herein، we report an extremely rare، or even perhaps a unique، patient from Iran. The clinical and skeletal findings were very unusual، with extensive clavarial، tubular، vertebral، ribs، and scapular overgrowth and synostosis. Indeed، the results of these abnormalities made a monstrous giant with a very tall stature. This is a unique case، which was living during 1912-1940 in Shiraz. The report’s information and photos، kindly supplied by Prof. Sheikholeslami. We evaluated thoroughly the findings together. Now we think; this is a very unusual case of its type، perhaps a Craniotubular Dysostosis Syndrome. We searched medical and clinical genetics literature، but did not find any similar case، having been reported before. So، to our knowledge، this is a unique case in the history of world medicine. We suggest to call this entity; “Siah-Khan syndrome” (after the patient’s name) ، or “Ghorban-Sheikholeslami-Shafeghati syndrome” (in honour of Prof. Ghorban who was recently has died، or “Cranio-Spondylo-Tubular Syndrome”.