The Experts below are selected from a list of 180 Experts worldwide ranked by ideXlab platform
Klaus Zerres - One of the best experts on this subject based on the ideXlab platform.
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Spinal Muscular Atrophies
Emery and Rimoin's Principles and Practice of Medical Genetics (Sixth Edition), 2013Co-Authors: Sabine Rudnikschoneborn, Klaus ZerresAbstract:The term Spinal Muscular atrophy (SMA) comprises a clinically and genetically heterogeneous group of diseases characterized by degeneration and loss of the anterior horn cells in the Spinal cord, and, depending on type and severity, sometimes also in the brainstem nuclei, resulting in muscle weakness and atrophy. The criteria used for the subdivision of the SMAs into separate entities are age of onset, severity, distribution of weakness, inclusion of additional features, and different modes of inheritance. Clinical diagnosis is established by the clinical presentation of symmetrical muscle weakness, normal or only mildly elevated creatine kinase values, neurogenic findings upon electromyography and muscle biopsy, while peripheral nerve function generally is normal. However, genetic screening has largely replaced invasive neurologic tests in the diagnosis of proximal SMA types I–III, the rare diaphragmatic type of SMA, and bulboSpinal neuronopathy (Kennedy syndrome). With respect to most of the nonproximal SMAs and autosomal dominant forms of SMAs, the genetic basis remains to be identified at the time of writing (February 2011). Despite improved understanding of the pathomechanisms in genetically identified forms, there is as yet no causal treatment of SMA.
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93rd enmc international workshop non 5q Spinal Muscular Atrophies sma clinical picture 6 8 april 2001 naarden the netherlands
Neuromuscular Disorders, 2003Co-Authors: Klaus Zerres, Sabine RudnikschonebornAbstract:This 93rd SMA workshop followed the European NeuroMuscular Centre (ENMC) tradition to combine clinical and molecular topics with the aim of not only exchanging current knowledge but also initiating collaborative studies. Despite important milestones in research on autosomal recessive SMA with localisation on chromosome 5q (SMA 5q) in the past 10 years, we are just beginning to understand the molecular basis and phenotypic spectrum of non-5q-SMA entities. The possibility of analysing the SMN gene allowed the delineation of the diagnostic criteria of ‘classical’ proximal SMA and its clinical variability. On the other hand, different entities of SMA could be defined that show atypical features and proved to be unlinked to chromosome 5q. The field of interest has therefore been focussed on further genes responsible for anterior horn cell loss. This will contribute to further understand the underlying pathogenetic pathways, the complex protein interactions and genotype–phenotype correlations in various types of motor neuron disorders. The workshop was structured in a first part, briefly reviewing the current status of SMA 5q including animal models which have been generated. The second part included different sessions on non-5q-SMA forms; clinical and diagnostic criteria were discussed and adapted to current knowledge. These were summarized by invited chairpersons (named in brackets) and followed by contributions of the participants. The following short summaries cover the essentials of the reviews, the discussion and the consensus achieved. 1. Update on SMA 5q
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no evidence for linkage of autosomal dominant proximal Spinal Muscular Atrophies to chromosome 5q markers
Human Genetics, 1991Co-Authors: Katrin Kausch, Sabine Rudnikschoneborn, C R Muller, T Grimm, Kenneth Ricker, Marcella Rietschel, Klaus ZerresAbstract:Two recent articles have reported the linkage of a gene for recessive Spinal Muscular atrophy (SMA) on the chromosome region 5q11.2–13.3. Our data show no linkage of the dominantly inherited forms of SMA to this chromosome region.
Sabine Rudnikschoneborn - One of the best experts on this subject based on the ideXlab platform.
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Spinal Muscular Atrophies
Emery and Rimoin's Principles and Practice of Medical Genetics (Sixth Edition), 2013Co-Authors: Sabine Rudnikschoneborn, Klaus ZerresAbstract:The term Spinal Muscular atrophy (SMA) comprises a clinically and genetically heterogeneous group of diseases characterized by degeneration and loss of the anterior horn cells in the Spinal cord, and, depending on type and severity, sometimes also in the brainstem nuclei, resulting in muscle weakness and atrophy. The criteria used for the subdivision of the SMAs into separate entities are age of onset, severity, distribution of weakness, inclusion of additional features, and different modes of inheritance. Clinical diagnosis is established by the clinical presentation of symmetrical muscle weakness, normal or only mildly elevated creatine kinase values, neurogenic findings upon electromyography and muscle biopsy, while peripheral nerve function generally is normal. However, genetic screening has largely replaced invasive neurologic tests in the diagnosis of proximal SMA types I–III, the rare diaphragmatic type of SMA, and bulboSpinal neuronopathy (Kennedy syndrome). With respect to most of the nonproximal SMAs and autosomal dominant forms of SMAs, the genetic basis remains to be identified at the time of writing (February 2011). Despite improved understanding of the pathomechanisms in genetically identified forms, there is as yet no causal treatment of SMA.
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93rd enmc international workshop non 5q Spinal Muscular Atrophies sma clinical picture 6 8 april 2001 naarden the netherlands
Neuromuscular Disorders, 2003Co-Authors: Klaus Zerres, Sabine RudnikschonebornAbstract:This 93rd SMA workshop followed the European NeuroMuscular Centre (ENMC) tradition to combine clinical and molecular topics with the aim of not only exchanging current knowledge but also initiating collaborative studies. Despite important milestones in research on autosomal recessive SMA with localisation on chromosome 5q (SMA 5q) in the past 10 years, we are just beginning to understand the molecular basis and phenotypic spectrum of non-5q-SMA entities. The possibility of analysing the SMN gene allowed the delineation of the diagnostic criteria of ‘classical’ proximal SMA and its clinical variability. On the other hand, different entities of SMA could be defined that show atypical features and proved to be unlinked to chromosome 5q. The field of interest has therefore been focussed on further genes responsible for anterior horn cell loss. This will contribute to further understand the underlying pathogenetic pathways, the complex protein interactions and genotype–phenotype correlations in various types of motor neuron disorders. The workshop was structured in a first part, briefly reviewing the current status of SMA 5q including animal models which have been generated. The second part included different sessions on non-5q-SMA forms; clinical and diagnostic criteria were discussed and adapted to current knowledge. These were summarized by invited chairpersons (named in brackets) and followed by contributions of the participants. The following short summaries cover the essentials of the reviews, the discussion and the consensus achieved. 1. Update on SMA 5q
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no evidence for linkage of autosomal dominant proximal Spinal Muscular Atrophies to chromosome 5q markers
Human Genetics, 1991Co-Authors: Katrin Kausch, Sabine Rudnikschoneborn, C R Muller, T Grimm, Kenneth Ricker, Marcella Rietschel, Klaus ZerresAbstract:Two recent articles have reported the linkage of a gene for recessive Spinal Muscular atrophy (SMA) on the chromosome region 5q11.2–13.3. Our data show no linkage of the dominantly inherited forms of SMA to this chromosome region.
Judith Melki - One of the best experts on this subject based on the ideXlab platform.
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Spinal Muscular Atrophies
Handbook of Clinical Neurology, 2013Co-Authors: Louis Viollet, Judith MelkiAbstract:Spinal Muscular Atrophies (SMA) are genetic disorders characterized by degeneration of lower motor neurons. The most frequent form is caused by mutations of the survival motor neuron 1 gene (SMN1). The identification of this gene greatly improved diagnostic testing and family-planning options of SMA families. SMN plays a key role in metabolism of RNA. However, the link between RNA metabolism and motor neuron degeneration remains unknown. A defect in mRNA processing likely generates either a loss of function of some critical RNA or abnormal transcripts with toxic property for motor neurons. Mutations of SMN in various organisms highlighted an essential role of SMN in motor axon and neuroMuscular junction development or maintenance. The quality of life of patients has greatly improved over recent decades through the improvement of care and management of patients. In addition, major advances in translational research have been made in the field of SMA. Various therapeutic strategies have been successfully developed aiming at acting on SMN2, a partially functional copy of the SMN1 gene which remains present in patients. Drugs have been identified and some are already at preclinical stages. Identifying molecules involved in the SMA degenerative process should represent additional attractive targets for therapeutics in SMA.
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de novo and inherited deletions of the 5q13 region in Spinal Muscular Atrophies
Science, 1994Co-Authors: Judith Melki, Suzie Lefebvre, Lydie Burglen, Philippe Burlet, Olivier Clermont, Philippe Millasseau, S Reboullet, B Benichou, Massimo Zeviani, Le D PaslierAbstract:Spinal Muscular Atrophies (SMAs) represent the second most common fatal autosomal recessive disorder after cystic fibrosis. Childhood Spinal Muscular Atrophies are divided into severe (type I) and mild forms (types II and III). By a combination of genetic and physical mapping, a yeast artificial chromosome contig of the 5q13 region spanning the disease locus was constructed that showed the presence of low copy repeats in this region. Allele segregation was analyzed at the closest genetic loci detected by markers C212 and C272 in 201 SMA families. Inherited and de novo deletions were observed in nine unrelated SMA patients. Moreover, deletions were strongly suggested in at least 18 percent of SMA type I patients by the observation of marked heterozygosity deficiency for the loci studied. These results indicate that deletion events are statistically associated with the severe form of Spinal Muscular atrophy.
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physical study of big fragments and search strategy of genes application to locus of infant Spinal Muscular Atrophies
Comptes rendus des séances de la Société de biologie et de ses filiales, 1994Co-Authors: Judith Melki, Suzie Lefebvre, Lydie Burglen, Philippe Burlet, Olivier Clermont, Philippe Millasseau, B Benichou, Massimo Zeviani, S Reboulet, Le Paslier DAbstract:Les amyotrophies Spinales (SMA) representent la maladie recessive autosomique fatale la plus frequente apres la mucoviscidose. Elles sont caracterisees par une degenerescence des motoneurones spinaux responsables d'un deficit musculaire avec amyotrophie. Les SMA de l'enfant sont classes en trois groupes (Type I, II, III) de gravite clinique decroissante. L'analyse genetique et physique de la region 5q13 a permis la construction d'un contig de chromosomes artificiels de levure (YAC) et a revele la presence d'elements repetes et specifiques de la region 5q13. Ces resultats ont fait rechercher la presence de deletions de cette region qui pourraient etre favorises par la survenue de crossing over entre ces elements. Deux cent une familles de SMA ont ete analysees avec les marqueurs polymorphes C212 et C272 et ont revele l'existence de deletions soit heritees, soit survenant de novo de la region 5q13. De plus, nous avons montre que ces deletions etaient plus frequentes dans les formes severes (Type I, 18%) que dans les formes moderees (Type III). Ces resultats constituent les premieres bases moleculaires des correlations entre le genotype aux loci etudies et le phenotype de la maladie
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gene for chronic proximal Spinal Muscular Atrophies maps to chromosome 5q
Nature, 1990Co-Authors: Judith Melki, Sonia Abdelhak, Peter Sheth, M F Bachelot, Peter Burlet, Alun Marcadet, J Aicardi, Alun Barois, J P Carriere, M FardeauAbstract:PROXIMAL Spinal Muscular Atrophies represent the second most common fatal, autosomal recessive disorder after cystic fibrosis1. The childhood form is classically subdivided into three groups: acute Werdnig-Hoffmann (type I), intermediate Werdnig-Hoffmann disease (type II) and Kugelberg-Welander disease (type III). These different clinical forms have previously been attributed to either genetic heterogeneity or variable expression of different mutations at the same locus2. Research has been hindered because the underlying biochemical defect is unknown, and there are insufficient large pedigrees with the most common and severe form (type I) available for study. Therefore, we have undertaken a genetic linkage analysis of the chronic forms of the disease (types II and III) as an initial step towards the ultimate goal of characterizing the gene(s) responsible for all three types. We report here the assignment of the locus for the chronic forms to the long arm of chromosome 5 (5q 12–ql4), with the anonymous DNA marker D5S39, in 24 multiplex families of distinct ethnic origin. Furthermore, no evidence for genetic heterogeneity was found for types II and III in our study, suggesting that these two forms are allelic disorders.
Hans Scheffer - One of the best experts on this subject based on the ideXlab platform.
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Best practice guidelines for molecular analysis in Spinal Muscular atrophy
European Journal of Human Genetics, 2001Co-Authors: Hans Scheffer, Jan Maarten Cobben, Gert Matthijs, Brunhilde WirthAbstract:With a prevalence of approximately 1/10 000, and a carrier frequency of 1/40–1/60 the proximal Spinal Muscular Atrophies (SMAs) are among the most frequent autosomal recessive hereditary disorders. Patients can be classified clinically into four groups: acute, intermediate, mild, and adult (SMA types I, II, III, and IV, respectively). The complexity and instability of the genomic region at chromosome 5q13 harbouring the disease-causing survival motor neuron 1 (SMN1) gene hamper molecular diagnosis in SMA. In addition, affected individuals with SMA-like phenotypes not caused by SMN1, and asymptomatic individuals with two mutant alleles exist. The SMN gene is present in at least one telomeric (SMN1) and one centromeric copy (SMN2) per chromosome in normal (non-carrier) individuals, although chromosomes containing more copies of SMN1 and/or SMN2 exist. Moreover, the two SMN genes (SMN1 and SMN2) are highly homologous and contain only five base-pair differences within their 3′ ends. Also, a relatively high de novo frequency is present in SMA. Guidelines for molecular analysis in diagnostic applications, carrier detection, and prenatal analysis using direct and indirect approaches are described. Overviews of materials used in the molecular diagnosis as well as Internet resources are included.
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linkage and apparent heterogeneity in proximal Spinal Muscular Atrophies
Neuromuscular Disorders, 1993Co-Authors: Jan Maarten Cobben, Hans Scheffer, Marianne De Visser, Jan Osinga, Rune R Frants, Gerrit Van Der Steege, C Wijmenga, Leo Ten P Kate, Gertjan B Van Ommen, Charles H C M BuysAbstract:Abstract Linkage studies with 9 highly informative DNA markers on the long arm of chromosome 5 were performed in 12 multiplex families (29 patients) with Spinal Muscular atrophy (SMA) from The Netherlands. The results of the linkage analysis were compatible with localization of a major SMA gene in the chromosomal region 5q12–13. By minimum recombinant analysis the most likely position of the SMA locus was between loci D5S6/D5S125 and D5S112/MAP1B, which is in agreement with several linkage studies from other countries. In four families, however, more than one crossover between SMA and a flanking DNA marker appeared, and in one family the observed hybridization phenotype for the markers closely flanking the SMA locus was identical for an unaffected individual and for his two affected sibs with SMA type III. For this latter family, among several explanations the most likely are either the presence of a double crossover or linkage heterogeneity.
Ashraf A Elharouni - One of the best experts on this subject based on the ideXlab platform.
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molecular prenatal diagnosis of autosomal recessive childhood Spinal Muscular Atrophies smas
Gene, 2012Co-Authors: Mona L Essawi, Ghada M Alattribi, Khaled R Gaber, Ashraf A ElharouniAbstract:Autosomal recessive childhood Spinal Muscular atrophy (SMAs) is the second most common neuroMuscular disorder and a common cause of infant disability and mortality. SMA patients are classified into three clinical types based on age of onset, and severity of symptoms. About 94% of patients have homozygous deletion of exon 7 in survival motor neuron (SMN1) gene. The neuronal apoptosis inhibitory protein (NAIP) gene was found to be more frequently deleted in the severest form of the disease. This study aimed to comment on the implementation of genetic counseling and prenatal diagnosis of SMAs for 85 fetuses from 75 Egyptian couples at risk of having an affected child. The homozygous deletion of exon 7 in SMN1 gene and the deletion of exon 5 of the NAIP gene were detected using PCR-REFLP and multiplex PCR methods respectively. Eighteen fetuses showed homozygous deletion of exon 7 in SMN1 gene and deletion of exon 5 in NAIP gene. In conclusion prenatal diagnosis is an important tool for accurate diagnosis and genetic counseling that help decision making in high risk families.
