The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Brunhilde Wirth - One of the best experts on this subject based on the ideXlab platform.
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quantitative analyses of smn1 and smn2 based on real time lightcycler pcr fast and highly reliable Carrier Testing and prediction of severity of spinal muscular atrophy
American Journal of Human Genetics, 2002Co-Authors: Markus Feldkotter, Verena Schwarzer, Radu Wirth, Thomas F Wienker, Brunhilde WirthAbstract:Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans, caused by homozygous absence of the survival motor neuron gene 1 (SMN1). SMN2, a copy gene, influences the severity of SMA and may be used in somatic gene therapy of patients with SMA in the future. We present a new, fast, and highly reliable quantitative test, based on real-time LightCycler PCR that amplifies either SMN1 or SMN2. The SMN1 copies were determined and validated in 329 Carriers and controls. The specificity of the test is 100%, whereas the sensitivity is 96.2%. The quantitative analysis of SMN2 copies in 375 patients with type I, type II, or type III SMA showed a significant correlation between SMN2 copy number and type of SMA as well as duration of survival. Thus, 80% of patients with type I SMA carry one or two SMN2 copies, and 82% of patients with type II SMA carry three SMN2 copies, whereas 96% of patients with type III SMA carry three or four SMN2 copies. Among 113 patients with type I SMA, 9 with one SMN2 copy lived
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quantitative analyses of smn1 and smn2 based on real time lightcycler pcr fast and highly reliable Carrier Testing and prediction of severity of spinal muscular atrophy
American Journal of Human Genetics, 2002Co-Authors: Markus Feldkotter, Verena Schwarzer, Radu Wirth, Thomas F Wienker, Brunhilde WirthAbstract:Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans, caused by homozygous absence of the survival motor neuron gene 1 (SMN1). SMN2, a copy gene, influences the severity of SMA and may be used in somatic gene therapy of patients with SMA in the future. We present a new, fast, and highly reliable quantitative test, based on real-time LightCycler PCR that amplifies either SMN1 or SMN2. The SMN1 copies were determined and validated in 329 Carriers and controls. The specificity of the test is 100%, whereas the sensitivity is 96.2%. The quantitative analysis of SMN2 copies in 375 patients with type I, type II, or type III SMA showed a significant correlation between SMN2 copy number and type of SMA as well as duration of survival. Thus, 80% of patients with type I SMA carry one or two SMN2 copies, and 82% of patients with type II SMA carry three SMN2 copies, whereas 96% of patients with type III SMA carry three or four SMN2 copies. Among 113 patients with type I SMA, 9 with one SMN2 copy lived <11 mo, 88/94 with two SMN2 copies lived <21 mo, and 8/10 with three SMN2 copies lived 33-66 mo. On the basis of SMN2 copy number, we calculated the posterior probability that a child with homozygous absence of SMN1 will develop type I, type II, or type III SMA.
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molecular analysis of spinal muscular atrophy and modification of the phenotype by smn2
Genetics in Medicine, 2002Co-Authors: Matthew D Mailman, Pamela J Snyder, John W Heinz, Mary S Sedra, Brunhilde Wirth, Arthur H.m. Burghes, Audrey C Papp, Thomas W. PriorAbstract:Purpose: This study describes SMN1 deletion frequency, Carrier studies, and the effect of the modifying SMN2 gene on the spinal muscular atrophy (SMA) phenotype. A novel allele-specific intragenic mutation panel increases the sensitivity of SMN1 Testing. Methods: From 1995 to 2001, 610 patients were tested for SMN1 deletions and 399 relatives of probands have been tested for Carrier status. SMN2 copy number was compared between 52 type I and 90 type III patients, and between type I and type III patients with chimeric SMN genes. A fluorescent allele-specific polymerase chain reaction (PCR) -based strategy detected intragenic mutations in potential compound heterozygotes and was used on 366 patients. Results: Less than half of the patients tested were homozygously deleted for SMN1. A PCR-based panel detected the seven most common intragenic mutations. SMN2 copy number was significantly different between mild and severely affected patients. Conclusions: SMN1 molecular Testing is essential for the diagnosis of SMA and allows for accurate Carrier Testing. Screening for intragenic mutations in SMN1 increases the sensitivity of diagnostic Testing. Finally, SMN2 copy number is conclusively shown to ameliorate the phenotype and provide valuable prognostic information.
Eduardo F. Tizzano - One of the best experts on this subject based on the ideXlab platform.
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two independent mutations of the smn1 gene in the same spinal muscular atrophy family branch lessons for Carrier diagnosis
Genetics in Medicine, 2006Co-Authors: M.j. Barceló, Laura Alias, Lidia Caselles, Yolanda Robles, M Baiget, Eduardo F. TizzanoAbstract:Purpose: We present the results of Carrier studies in 33 relatives of the paternal branch of a spinal muscular atrophy patient with homozygous absence of the SMN1 gene. Methods and Results: Once linkage and quantitative analyses were performed, a number of first-, second- and third-degree relatives were identified as Carriers given that they shared the at-risk haplotype and showed one SMN1 copy. In the fourth-degree relatives, linkage analysis demonstrated discordance with the quantitative results because the members with one copy were Carriers of the mutation, but in a different haplotype background. We concluded that two independent mutations were present in this branch of the family. Furthermore, the combination of both methods of analysis allowed us to identify Carriers with two SMN1 genes in one chromosome and none in the remaining chromosome. Conclusions: Carrier Testing in spinal muscular atrophy should be performed by employing both quantitative and linkage analyses in order to guarantee accurate Carrier identification.
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Implementation of SMA Carrier Testing in genetic laboratories: comparison of two methods for quantifying the SMN1 gene.
Human Mutation, 2002Co-Authors: Ivon Cuscó, M.j. Barceló, Montserrat Baiget, Eduardo F. TizzanoAbstract:The degeneration and loss of motor neurons of the anterior horn characterize children affected with spinal muscular atrophy (SMA). Mutations in the survival motor neuron gene (SMN1) are determinant for the development of the disease whereas the number of copies of SMN2, the highly homologous copy of SMN1, plays a role as a phenotypic modifier factor. The detection of SMN1 homozygous deletions is the typical test for SMA diagnosis. Owing to the limitation of this test for Carrier and heterozygous deletion analysis, the demand of SMN1 quantitative tests is permanently growing. The high incidence of SMA, the notable Carrier frequency, the severity of the disease, and the lack of effective treatment may justify the implementation of such an analysis in DNA diagnostic labs. The advantages and disadvantages of two reliable quantitative methods were evaluated. One of these is a competitive PCR protocol using internal standards and a genomic sequence as a reference. The other method is a real-time PCR employing an external standard as a reference. Both methods present sufficient advantages for incorporation into molecular genetic diagnostic labs. The possibility of studying samples from different labs, the versatility and reproducibility of the analysis, and cost-benefit calculations must be considered in the final choice.
Markus Feldkotter - One of the best experts on this subject based on the ideXlab platform.
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quantitative analyses of smn1 and smn2 based on real time lightcycler pcr fast and highly reliable Carrier Testing and prediction of severity of spinal muscular atrophy
American Journal of Human Genetics, 2002Co-Authors: Markus Feldkotter, Verena Schwarzer, Radu Wirth, Thomas F Wienker, Brunhilde WirthAbstract:Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans, caused by homozygous absence of the survival motor neuron gene 1 (SMN1). SMN2, a copy gene, influences the severity of SMA and may be used in somatic gene therapy of patients with SMA in the future. We present a new, fast, and highly reliable quantitative test, based on real-time LightCycler PCR that amplifies either SMN1 or SMN2. The SMN1 copies were determined and validated in 329 Carriers and controls. The specificity of the test is 100%, whereas the sensitivity is 96.2%. The quantitative analysis of SMN2 copies in 375 patients with type I, type II, or type III SMA showed a significant correlation between SMN2 copy number and type of SMA as well as duration of survival. Thus, 80% of patients with type I SMA carry one or two SMN2 copies, and 82% of patients with type II SMA carry three SMN2 copies, whereas 96% of patients with type III SMA carry three or four SMN2 copies. Among 113 patients with type I SMA, 9 with one SMN2 copy lived
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quantitative analyses of smn1 and smn2 based on real time lightcycler pcr fast and highly reliable Carrier Testing and prediction of severity of spinal muscular atrophy
American Journal of Human Genetics, 2002Co-Authors: Markus Feldkotter, Verena Schwarzer, Radu Wirth, Thomas F Wienker, Brunhilde WirthAbstract:Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans, caused by homozygous absence of the survival motor neuron gene 1 (SMN1). SMN2, a copy gene, influences the severity of SMA and may be used in somatic gene therapy of patients with SMA in the future. We present a new, fast, and highly reliable quantitative test, based on real-time LightCycler PCR that amplifies either SMN1 or SMN2. The SMN1 copies were determined and validated in 329 Carriers and controls. The specificity of the test is 100%, whereas the sensitivity is 96.2%. The quantitative analysis of SMN2 copies in 375 patients with type I, type II, or type III SMA showed a significant correlation between SMN2 copy number and type of SMA as well as duration of survival. Thus, 80% of patients with type I SMA carry one or two SMN2 copies, and 82% of patients with type II SMA carry three SMN2 copies, whereas 96% of patients with type III SMA carry three or four SMN2 copies. Among 113 patients with type I SMA, 9 with one SMN2 copy lived <11 mo, 88/94 with two SMN2 copies lived <21 mo, and 8/10 with three SMN2 copies lived 33-66 mo. On the basis of SMN2 copy number, we calculated the posterior probability that a child with homozygous absence of SMN1 will develop type I, type II, or type III SMA.
Martin B Delatycki - One of the best experts on this subject based on the ideXlab platform.
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ethical considerations in choosing a model for population based cystic fibrosis Carrier screening
The Medical Journal of Australia, 2010Co-Authors: Lucy J Modra, John R Massie, Martin B DelatyckiAbstract:Cystic fibrosis (CF) Carrier Testing can be used to inform reproductive decision making, allowing Carriers to avoid having a child with CF. A government-funded, population-based CF Carrier screening program would allow greater equity of access to this test. The setting in which CF Carrier screening is offered significantly affects the extent to which participants make well informed, voluntary decisions to accept or decline Testing. Screening offered before pregnancy and in non-clinical environments better promotes participant autonomy than screening offered in the prenatal consultation.
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evaluation of a tay sachs disease screening program
Clinical Genetics, 2003Co-Authors: A A Gason, Sylvia A Metcalfe, Maryanne Aitken, Edith Sheffield, Agnes Bankier, Barlow K Stewart, Martin B DelatyckiAbstract:Tay-Sachs Disease (TSD) is an autosomal recessive neurodegenerative disorder. TSD is prevalent in the Ashkenazi Jewish population, and Carrier screening programs have been implemented worldwide in these communities. A screening program initiated in 1997 involving the Melbourne Jewish community (Australia) incorporated education, counselling and Carrier Testing of high-school students aged 15 to 18 years. This study aimed to assess the participation rates, level of knowledge obtained and predicted feelings and attitudes of the students involved. Seven hundred and ten students participated, there was a 67% uptake for Testing with a Carrier rate of 1 in 28 determined. The level of knowledge of the students following education was high and of relative importance in regard to decision making, as were their feelings and attitudes about genetic Testing for Carrier status. A significant impediment to test uptake was the need for blood sampling, resulting in a recommendation for the introduction of DNA analysis on cheek brush samples. The evaluation of this program has given a wider scope for further development as well as providing valuable information for the implementation of community screening programs.
Thomas F Wienker - One of the best experts on this subject based on the ideXlab platform.
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quantitative analyses of smn1 and smn2 based on real time lightcycler pcr fast and highly reliable Carrier Testing and prediction of severity of spinal muscular atrophy
American Journal of Human Genetics, 2002Co-Authors: Markus Feldkotter, Verena Schwarzer, Radu Wirth, Thomas F Wienker, Brunhilde WirthAbstract:Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans, caused by homozygous absence of the survival motor neuron gene 1 (SMN1). SMN2, a copy gene, influences the severity of SMA and may be used in somatic gene therapy of patients with SMA in the future. We present a new, fast, and highly reliable quantitative test, based on real-time LightCycler PCR that amplifies either SMN1 or SMN2. The SMN1 copies were determined and validated in 329 Carriers and controls. The specificity of the test is 100%, whereas the sensitivity is 96.2%. The quantitative analysis of SMN2 copies in 375 patients with type I, type II, or type III SMA showed a significant correlation between SMN2 copy number and type of SMA as well as duration of survival. Thus, 80% of patients with type I SMA carry one or two SMN2 copies, and 82% of patients with type II SMA carry three SMN2 copies, whereas 96% of patients with type III SMA carry three or four SMN2 copies. Among 113 patients with type I SMA, 9 with one SMN2 copy lived
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quantitative analyses of smn1 and smn2 based on real time lightcycler pcr fast and highly reliable Carrier Testing and prediction of severity of spinal muscular atrophy
American Journal of Human Genetics, 2002Co-Authors: Markus Feldkotter, Verena Schwarzer, Radu Wirth, Thomas F Wienker, Brunhilde WirthAbstract:Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans, caused by homozygous absence of the survival motor neuron gene 1 (SMN1). SMN2, a copy gene, influences the severity of SMA and may be used in somatic gene therapy of patients with SMA in the future. We present a new, fast, and highly reliable quantitative test, based on real-time LightCycler PCR that amplifies either SMN1 or SMN2. The SMN1 copies were determined and validated in 329 Carriers and controls. The specificity of the test is 100%, whereas the sensitivity is 96.2%. The quantitative analysis of SMN2 copies in 375 patients with type I, type II, or type III SMA showed a significant correlation between SMN2 copy number and type of SMA as well as duration of survival. Thus, 80% of patients with type I SMA carry one or two SMN2 copies, and 82% of patients with type II SMA carry three SMN2 copies, whereas 96% of patients with type III SMA carry three or four SMN2 copies. Among 113 patients with type I SMA, 9 with one SMN2 copy lived <11 mo, 88/94 with two SMN2 copies lived <21 mo, and 8/10 with three SMN2 copies lived 33-66 mo. On the basis of SMN2 copy number, we calculated the posterior probability that a child with homozygous absence of SMN1 will develop type I, type II, or type III SMA.