Genotype-phenotype correlation in patients with Familial Mediterranean Fever: Evaluation of E148Q and M694V mutations

Familial Mediterranean Fever [FMF] is an autosomal recessive disorder characterized by self-limited episodes of fevere and painful recurrent polyserositis that predominantly affects Mediterranean races. In recent years some reports have shown high prevalence of FMF in North-west Iran, with M694V and E148Q being most frequent reported mutations. The aim of this study is to evaluate the clinical manifestations of FMF in patients with these mutations. A cross sectional- descriptive study was performed in a 1 year period [January 2007. January 2008] 71 patients younger than 18 years with clinical diagnosis of disease proved in Children Hospital of Tabriz-Iran were referred to genetic lab for mutation analysis. ARMS-PCR and PCR-RFLP were used to detect mutations. Only 45 patients were shown to have identified mutations and 41 patients among them had M694V and E148Q mutations which were assessed for various clinical manifestations. M694V and E148Q mutations were seen in 55.7 and 35.5 patients respectively. Patients homozygous for M694V were found to have earlier age of onset, longer duration of attacks, higher prevalence of positive family history and more complications. In our patients, prevalence of some manifestations differed from other ethnic groups reported previously. M694V mutation in FMF patients especially in homozygous state is accompanied with more severe disease and more complications

[Clinical, electrophysiologic and genetic characteristics of childhood onset spinal muscular atrophy]

Spinal muscular atrophy[SMA] is one of the most common autosomal recessive disorders characterized by degeneration of anterior born cells in the spinal cords and leads to progressive muscular weakness and atrophy. The last 10 years have seen major advances in the field of diagnosis of SMA, but no curative treatment is available now. This study aimed to analyze the clinical characteristics of different types of SMA, improve the clinical diagnosis of SMA and prenatal diagnosis of SMA by gene analysis. Patients with SMA were recruited from neurologic clinic from January 2004 to March 2006. The diagnosis of SMA was made from clinical history and examination, electro physiologic assessment or molecular studies. The clinical characteristics and changes of electrophysiology were assessed in all patients. The deletion of survival motor neuron [SMN] and neuronal apoptosis inhibitory protein [NAIP] genes was studied by PCR. Based on age of onset, age of death, achievement of motor milestones and ambulatory status patients classified into SMA I, SMA II and SMA III. The 42 patients, including 28[66.7%] males and 14[33.3%] females were enrolled in this study. The patients were subdivided into clinical groups: 30 [71.7%] of case with SMA I 9[21.4%] of cases with SMA II, 2[4.8%] of case with SMA III and 1[2.4%] of cases with SMA diaphragmatic. They were all characterized by symmetric muscle weakness [more proximal than distal] associated with atrophy, absence or marked decrease of deep tendon reflexes. Fasciculation of tongue was noted in 59.5% of patients. Electroghsiologic studies showed a neurogenic pattern with denervation potentials on 92.8% of cases. The SMN gene was deleted in 78.5% of patients and the NAIP gene was deleted in 54.8% of cases. Deletion of NAIP gene was more common in SMA I, and its deletion correlated with the severity of diseases [P=0.011]. The definite diagnosis of SMA will relay on typical clinical characteristics and changes of electrophysiologic study and gene deletion gene. Genetic diagnosis of SMA can provide a basis of prenatal diagnosis of SMA

[Association analysis of autosomal dominant polycystic kidney disease in familial type in East-Azerbaijan]

Familial form of polycystic kidney disease which is inherited as an autosomal dominant pattern is one of the most common form of kidney disease. The main manifestation of this disease is the presence of growing cysts in kidney which results in malfunction of kidney. The frequency of disease is one in 1000 living birth. Mutation in one of the three different genes could result in developing polycystic kidney disease. Genetically analysis has been able to identify two of the genes, PKD1 and PKD2, located on chromosome 16 and chromosome 4 respectively. The location of the third gene remains unrevealed and the frequency of families affected due to the mutation on this gene is very low. By applying microsatellites tightly linked to the identified polycystic kidney disease genes, affected families referred from East Azerbaijan were genetically analyzed. Families with at least three affected members by polycystic kidney disease were studied. Polymorphic microsatellites from the regions of PKD1 and PKD2 were selected by studying the members of these families. All members of the families were investigated by the polymorphic markers to study linkage analysis. Out of 13 families with 99 members referred by specialists, 7 families with 75 members were selected on the base of availability. Disease in three of these families showed linkage with PKD2 gene and in one family linkage was found between the disease and PKD1 gene. In another family linkage was observed with neither PKD1 nor PKD2 genes. None of the markers were informative in two of the families; therefore these families were excluded from the studies. Most of the families with polycystic kidney disease from North West of Iran, showed linkage with PKD2 gene. One of the families did not show linkage with any of the known genes. In this family, disease could be due to mutation in the third gene which remains to be identified

[Genetic assessment of chromosome 21 microsatellites and their application in the diagnosis of down syndrome patients within an Eastern Azarbayjan population]

Down syndrome is one of the most common chromosome aneuploidies causing mental retardation which occurs in approximately 1/230 pregnancies. It is usually caused by the presence of an extra chromosome 21. The aim of this study was to evaluate the simple PCR based DNA diagnostic method and also to determine the parental origin of the extra chromosome 21 in trisomal Down syndrome. To determine the polymorphism rates of chromosome 21 microsatellite markers, 50 people from Eastern Azarbayjan were randomly selected and studied for the microsatellites. The results were statistically analyzed. Thirty affected Down syndrome patients, diagnosed by specialists were referred to the lab for further molecular analysis. After genetic counseling and getting consent, blood samples were obtained. Seven pairs of chromosome 21 microsatellite markers were amplified using PCR in all the samples. Five highly polymorphic microsatellite markers were selected from a total seven markers, studied in 50 normal people. Out of 30 Down syndrome's patients, trisomal 21 was diagnosed in 21 families [70%]. In which non-disjunction errors were determined to be of maternal origin in 86% and of paternal origin in 9% of the cases. The mean maternal and parental age was 33/3 and 36/2, respectively. The three microsatellite markers, D21S1910, D21S1411 and D21S11 could diagnose a high percentage of trisomal 21 in Down syndrome' patients. The parental origin of an extra copy of chromosome 21 could be exactly determined

[Detection of suspected duchenne muscular dystrophy carriers by microsatellite markers application]

Duchenne Muscular Dystrophy[DMD] is a neuromuscular disorder with progressive muscle wasting and weakness. This disease is the consequence of mutations in dystrophin gene located on X chromosome. Inheritance pattern of the disease is gene-dependent recessive with an incidence of one in 3500 alive male newborns. Due to the absence of efficient treatment, detection of female carriers is essential for genetic counselling and prenatal diagnosis. 14 DMD families were referred to the genetic laboratory by specialists. DNA was extracted from the whole peripheral blood and analyzed by gene tracking technique. All members of the families were studied through 7 microsatellites located in and around dystrophin gene. 37 females at the risk of being DMD carriers and 7 obligate carriers were studied and ultimately 27 females [72.97%] were identified as carriers or non-carriers. In the families who were diagnosed as DMD patients by clinical and preclinical procedure's gene tracking is a reliable and less expensive technique for female carrier-status identification with a 95-100% confidence

Diagnosis and screening of spinal-muscular atrophy type III disease through PCR-RFLP in East Azarbaijan during 2004-2005

Hereditary pattern of spinal-muscular atrophy [SMA] disease is in form of recessive autosome with a frequency of 1 in 10000 live births. In most of the patients SMN1 gene bears deletions in exons 7 or 8. The aim of this study is to investigate deletion of above mentioned gene through molecular techniques in east Azarbaigan during 2004-2005. The patients likely to have SMA type III were referred to molecular study following the clinical and laboratory diagnosis. After extraction of DNA from patients' blood the extent of deletion in exons 7 and 8 of SMN1 gene, was investigated through PCR-Restriction Fragment Length Polymorphism [RFLP]. Out of 45 patients likely to have SMA type III, 9 people [20%] had exon deletion in SMN1 gene among whom one patient bore deletion only in exon 7 while the rest bore deletion in both exons [7, 8] of SMN1 gene. Deletion in SMN1 gene was observed in a low percent of the patients likely to have SMA type III. More research including the other sequences of SMN1 gene is recommended