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SMN1 Gene (smn1 + gene)
Selected AbstractsQuantification of SMN1 and SMN2 genes by capillary electrophoresis for diagnosis of spinal muscular atrophyELECTROPHORESIS, Issue 13 2008Chun-Chi Wang Abstract We present the first CE method for the separation and quantification of SMN1 and SMN2 genes. Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder deleted or mutated in SMN1 gene and retained at least one copy of SMN2 gene. However, these two genes are highly homologous, differentiation and quantification of SMN1 and SMN2 are therefore required in diagnosis to identify SMA patients and carriers. We developed a fluorescence-labeled conformation-sensitive CE method to quantitatively analyze PCR products covering the variable position in the SMN1/SMN2 genes using a copolymer solution composed of hydroxyethylcellulose and hydroxypropylcellulose. The DNA samples included 24 SMA patients, 52 parents of SMA patients (obligatory carriers), and 255 controls. Those 331 samples were blind analyzed to evaluate the method, and the results compared with those obtained using denaturing HPLC (DHPLC). Validation of accuracy was performed by comparing the results with those of DHPLC. Nine of total samples showed different results. Diagnosis of one fetus DNA among them was related to abortion or not, which was further confirmed by gel electrophoresis and DNA sequencing. Our method showed good coincidence with them, and proved the misdiagnosis of DHPLC. This simple and reliable CE method is a powerful tool for clinical genotyping of large populations to detect carriers and SMA patients. [source] Carrier frequency of SMA by quantitative analysis of the SMN1 deletion in the Iranian populationEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2010M. Hasanzad Background and purpose:, Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder. Carrier frequency studies of SMA have been reported for various populations. Although no large-scale population-based studies of SMA have been performed in Iran, previous estimates have indicated that the incidence of autosomal recessive disorder partly because of the high prevalence of consanguineous marriage is much higher in the Iranian population than in other populations. Methods:, In this study, we used a reliable and highly sensitive quantitative real-time PCR assay with SYBR green I dye to detect the copy number of the SMN1 gene to determine the carrier frequency of SMA in 200 healthy unrelated, non-consanguineous couples from different part of Iran. Results:, To validate the method in our samples, we determined the relative quantification (RQ) of patients with homozygous deletion (0.00) and hemyzygous carriers (0.29,0.55). The RQ in 10 of 200 normal individuals were within the carrier range of 0.31,0.57, estimating a carrier frequency of 5% in the Iranian population. Conclusions:, Our data show that the SMA carrier frequency in Iran is higher than in the European population and that further programs of population carrier detection and prenatal testing should be implemented. [source] Spinal muscular atrophy: Recent advances and future prospectsMUSCLE AND NERVE, Issue 1 2002Sophie Nicole PhD Abstract Spinal muscular atrophies (SMA) are characterized by degeneration of lower motor neurons associated with muscle paralysis and atrophy. Childhood SMA is a frequent recessive autosomal disorder and represents one of the most common genetic causes of death in childhood. Mutations of the SMN1 gene are responsible for SMA. The knowledge of the genetic basis of SMA, a better understanding of SMN function, and the recent generation of SMA mouse models represent major advances in the field of SMA. These are starting points towards understanding the pathophysiology of SMA and developing therapeutic strategies for this devastating neurodegenerative disease, for which no curative treatment is known so far. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 4,13, 2002 [source] Molecular analysis of the SMN and NAIP genes in Iranian spinal muscular atrophy patientsPEDIATRICS INTERNATIONAL, Issue 2 2009Omid Omrani Abstract Background:, Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of spinal cord anterior horn cells, leading to muscular atrophy. SMA is clinically classified into three subgroups based on the age of onset and severity. The majority of patients with SMA have homozygous deletions of exons 7 and 8 of the survival motor neuron (SMN) gene. The purpose of the present study was to determine the frequency of SMN and neuronal apoptosis inhibitory protein (NAIP) gene deletions in Iranian SMA patients. Experience in prenatal diagnosis of SMA in this population is also reported. Methods:, To study the frequency of deletions of SMN and NAIP genes in an Iranian sample group, 75 unrelated SMA patients (54 type I, eight type II and 13 type III) were analyzed according to the methods described by van der Steege et al and Roy et al. Results:, Homozygous deletion of SMN1 exons 7 and/or 8 were identified in 68 out of 75 patients (90%). Deletion of exon 5 of the NAIP gene was found in 40/54 of type I, 2/8 of type II and 1/13 of type III patients. Conclusions:, Deletion of the SMN1 gene is a major cause of SMA in Iran, and NAIP gene deletions were common in the present patients with type I SMA. Also, the incidence of NAIP deletion is higher in more severe SMA. [source] C117T variant in the SMN1 gene found in the Japanese populationPEDIATRICS INTERNATIONAL, Issue 1 2007AHMAD HAMIM SADEWA Abstract Background: The SMN genes are closely related to the development of spinal muscular atrophy (SMA); mutated SMN1 causes SMA and functional SMN2 modifies the severity of SMA. SMN1 and SMN2 are almost identical, being distinguished by only five base pair substitutions located at the 3'-end of the genes. Recently, a synonymous DNA variant, C117T, has been identified at the first codon of SMN2 exon 2a in the Caucasian population. It is still a question whether the variant is specific to the Caucasian population, and whether it is found only in SMN2. In order to address these questions, Japanese populations were screened for the presence of C117T in the SMN genes. Methods: To detect the C117T variant in a Japanese population, polymerase chain reaction,restriction fragment length polymorphism was performed in 33 SMA patients homozygous for SMN1 deletion and 106 control individuals. Reverse transcription,polymerase chain reaction (RT-PCR) was performed to clarify whether the variant affects the splicing process of the SMN1 gene. Results: The C117T variant was found in one out of 33 Japanese SMA patients (3.0%) and in seven out of 106 Japanese control individuals (6.6%). There was no significant difference between frequencies in the present data and those reported from the Caucasian population. Notably, the C117T variant was also detected in the SMN1 gene; a control individual with homozygous SMN2 deletion was found to have the variant on one of the SMN1 genes. RT-PCR indicated that this variant of the SMN1 gene was normally transcribed and did not affect the splicing process in this individual. Conclusions: The C117T variant was found not only in the Caucasian population, but also in the Japanese population. In addition, the variant was not specific to SMN2: it was also found in SMN1. RT-PCR indicated that the variant did not affect the splicing process. [source] Prenatal diagnosis of spinal muscular atrophy: Indian scenarioPRENATAL DIAGNOSIS, Issue 8 2005Akanchha Kesari Abstract Objectives To study the psychosocial issues associated with prenatal diagnosis of SMA in India and the use of SMN1 copy number analysis for carrier detection prior to offering prenatal diagnosis. Methods Homozygous deletion of SMN1 gene was done by PCR-RFLP. Copy number analysis of SMN1 gene was performed by quantitative PCR. Results We report our experience of eight cases of prenatal diagnosis for SMA and the use of carrier detection prior to offering prenatal diagnosis. Quantitative PCR results show that SMN1 copy number analysis is useful to identify couples at risk. Conclusion Case analyses depict unique psychosocial issues associated with prenatal diagnosis of SMA from India. Copyright © 2005 John Wiley & Sons, Ltd. [source] Prenatal diagnosis for risk of spinal muscular atrophyBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 11 2002I. Cuscó Objectives Prenatal diagnosis of spinal muscular atrophy is usually performed in high risk couples by detection of a homozygous deletion in the survival motor neurone gene (SMN1). However, other relatives at risk of being carriers very often request genetic counselling and the possibility of prenatal diagnosis. The aim of this study was to validate a SMN1 gene quantitative test to help the couples formed by one spinal muscular atrophy carrier and a partner of the general population (1/200 potential risk) to achieve a less ambiguous risk result for the pregnancy. Design Spinal muscular atrophy carrier studies in at-risk individuals. Setting Department of Genetics and Gynaecology and Obstetrics in a large university hospital. Population Seventy-nine obligate carriers (more than one affected child with deletion in the offspring) and 58 non-carriers (relatives of spinal muscular atrophy families defined by marker studies) were tested to set up a quantitative analysis. The method was applied in different situations in 126 members from 34 families with spinal muscular atrophy patients. Methods DNA studies of the SMN1 gene by marker analysis and quantitative assay. Main outcome measures To determine double (non-carrier) or single dose (carrier) of exon 7 of the SMN1 gene in relatives of spinal muscular atrophy patients. Bayesian calculation of risk. Results The sensitivity and specificity of the method were 96% and 100%, respectively. Studies on different couples with an a priori risk of 1/200 allowed us to reduce the final risk to 1/5000 or to increase it to 1/4. Conclusions The quantitative method can be used to achieve a less ambiguous risk in pregnancies with a 1/200 risk and in families where no sample is available to study the index case. Screening of gamete donors when the recipient is a known carrier should also be considered. [source] C117T variant in the SMN1 gene found in the Japanese populationPEDIATRICS INTERNATIONAL, Issue 1 2007AHMAD HAMIM SADEWA Abstract Background: The SMN genes are closely related to the development of spinal muscular atrophy (SMA); mutated SMN1 causes SMA and functional SMN2 modifies the severity of SMA. SMN1 and SMN2 are almost identical, being distinguished by only five base pair substitutions located at the 3'-end of the genes. Recently, a synonymous DNA variant, C117T, has been identified at the first codon of SMN2 exon 2a in the Caucasian population. It is still a question whether the variant is specific to the Caucasian population, and whether it is found only in SMN2. In order to address these questions, Japanese populations were screened for the presence of C117T in the SMN genes. Methods: To detect the C117T variant in a Japanese population, polymerase chain reaction,restriction fragment length polymorphism was performed in 33 SMA patients homozygous for SMN1 deletion and 106 control individuals. Reverse transcription,polymerase chain reaction (RT-PCR) was performed to clarify whether the variant affects the splicing process of the SMN1 gene. Results: The C117T variant was found in one out of 33 Japanese SMA patients (3.0%) and in seven out of 106 Japanese control individuals (6.6%). There was no significant difference between frequencies in the present data and those reported from the Caucasian population. Notably, the C117T variant was also detected in the SMN1 gene; a control individual with homozygous SMN2 deletion was found to have the variant on one of the SMN1 genes. RT-PCR indicated that this variant of the SMN1 gene was normally transcribed and did not affect the splicing process in this individual. Conclusions: The C117T variant was found not only in the Caucasian population, but also in the Japanese population. In addition, the variant was not specific to SMN2: it was also found in SMN1. RT-PCR indicated that the variant did not affect the splicing process. [source] | |||||||||||||