Investigation of genetic causes of intellectual disability in Kerman province, south east of Iran

Intellectual disability [ID] has a worldwide prevalence of 1-3% and results from extraordinary heterogeneous. To shed more light on the causes of ID in Kerman Province, in Southeast Iran, we set out in 2008 to perform systematic clinical studies and homozygosity mapping in large Iranian families with ID. Fifty seven families with a minimum of two mentally retarded children from Kerman Province were initially tested for metabolic disorders, by Tandem mass spectrometry. Fragile X testing and standard karyotyping were performed for all probands of families. Cases with autosomal recessive [AR] pattern of inheritance and microcephaly were subjected to homozygosity mapping by using several microsatellite markers for known MCPH loci. Three out of seven families with X-linked pattern of inheritance were positive for fragile X syndrome. Chromosome abnormality was not observed in any of dysmorphic patients and all families were negative for metabolic tests. Among the remaining 50 families of AR ID, six were found to be microcephalic, of which 2 linked to two MCPH loci [33.3%]. The rest 4 families were not linked to any of the known loci. The results of this study showed that ID with microcephaly comprised 12% of ID cases in Kerman Province. In two families with apparent linkage to the MCPH5 and MCPH6 locus, mutation screening was not successful, which might indicate that either the mutation is located in the regulatory sequences of the gene or that there might be another genes present in these regions, which is mutated in such cases

Clinical and molecular aspects of Sjogren-Larsson syndrome reported in an iranian consanguineous family with triplet affected individuals

Sjogren Larsson Syndrome [SLS; OMIM: 270200] is an autosomal recessive neurocutaneous disorder characterized by mental retardation, congenital ichthyosis and spastic paraplegia. SLS is caused by mutations in aldehyde dehydrogenase 3A2 isoform 2 [ALDH3A2], which encodes fatty aldehyde dehydrogenase [FALDH]. This enzyme metabolizes the NAD-dependent oxidation of long chain aldehyde derived from lipid metabolism. Up to now, more than 72 mutations have been reported in SLS patients. DNA was extracted from peripheral blood of all the five patients, one healthy sibling and their parents using standard procedures. SNP genotyping was performed using the GeneChip [registered sign]. Multipoint linkage analyses and non-parametric linkage analysis was performed too. Results: Here, we report an interesting family with five affected individuals with a novel splice site mutation [c.1107+1delGTA] in ALDH3A2. In absence of capability to measure FALDH activity in Iran, DNA sequencing of the ALDH3A2 gene could lead to the identification of causative mutation and confirm the diagnosis

Evaluating the effect of DMSO concentrations on y-globin expression in Hull cells

Evaluating the effect of DMSO concentrations on g-globin expression in Hu11 cells Asgharian AM1, Banan M2, Deilami Z1, Gharesouran J3, Ghasemi S4, Behjati F2, Javadi GR5, Kahrizi K6, Najmabadi H7 1 PhD Student of cell and molecular biology, Department of Biology, Islamic Azad University, Science and Research Branch, Tehran, Iran. 2 Assistant professor, Genetics Research Center, University of Social Welfare and Rehabilitation Sciences. Tehran, Iran. 3 Student of MSc of Genetics, Genetics Research Center, University of Social Welfare and Rehabilitation Sciences. Tehran, Iran. 4 MSc of Genetics,Genetics Research Center, University of Social Welfare and Rehabilitation Sciences. Tehran, Iran. 5 Associate Professor, Department of Biology, Islamic Azad University, Science and Research Campus, Tehran, Iran. 6 Associate Professor, Genetics Research Center, University of Social Welfare and Rehabilitation Sciences. Tehran, Iran. 7 Professor, Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran Abstract Background: Understanding of the mechanisms involved in gamma- to beta-globin switching may be important for development of treatment options for b-thalassemia. Such studies require the availability of relevant cellular model systems. One such cell type is Hu11, a mouse erythroleukemia [MEL] cell line containing the human b-locus. MEL and Hu11 cells differentiate in the presence of the chemical dimethyl sulfoxide [DMSO]. Nevertheless, levels of gamma-globin induction in Hu11 cells after DMSO treatment have not been determined. In the present study, we determined gamma-globin levels in Hu11 cells after treatment with various DMSO concentrations. Materials and methods: Hu11 cells were cultivated in various DMSO concentrations and the levels of gamma-globin were determined by real-time PCR. Results: Our study showed that hemoglobin in Hu11 cells treated with 1% and 2% DMSO was increased by approximately 5 and 10 folds. Moreover real-time PCR results showed that g-globin levels using the indicated DMSO levels were increased by 66 and 298 folds, respectively. Hu11 cells differentiate in the presence of DMSO, and in doing so, their gamma-globin levels are increased. Therefore these cells can be used to study the mechanisms of gamma-globin induction. Such studies may be beneficial for the treatment of beta-thalassemia