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Guy A Rouleau - One of the best experts on this subject based on the ideXlab platform.
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Mutational analysis of neurotensin in familial restless legs syndrome
Movement disorders : official journal of the Movement Disorder Society, 2003Co-Authors: Alex Desautels, Gustavo Turecki, Jacques Montplaisir, Lan Xiong, Daniel Rochefort, Guy A RouleauAbstract:A susceptibility locus for restless legs syndrome (RLS) has been identified recently on Chromosome 12q. This region contains several transcribed genes including neurotensin (NTS), which, as an important modulator of the dopaminergic transmission, represents a strong functional and positional candidate in the context of RLS. In this study, NTS was evaluated for mutational analysis. A panel of 19 individuals from 4 families supporting linkage to 12q was investigated using a combined denaturing high-performance liquid chromatography (dHPLC) and direct sequencing method. Analysis of the NTS genomic sequence revealed 2 intronic polymorphisms and 1 variant located in the 5' untranslated region (UTR). None of the observed variants co-segregated with RLS and no disease-associated polymorphisms were detected in any of the analyzed families. Based on these results, it is unlikely that NTS is the gene responsible for RLS in Chromosome 12-linked families.
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identification of a major susceptibility locus for restless legs syndrome on Chromosome 12q
American Journal of Human Genetics, 2001Co-Authors: Alex Desautels, Gustavo Turecki, Jacques Y Montplaisir, Adolfo Sequeira, Andrei Verner, Guy A RouleauAbstract:Restless legs syndrome (RLS) is a neurological disorder characterized by leg paresthesia associated with an irresistible urge to move that often interferes with nocturnal sleep, leading to chronic sleep deprivation. To map genes that may play a role in the vulnerability to RLS, a genomewide scan was conducted in a large French-Canadian family. Significant linkage was established on Chromosome 12q, for a series of adjacent microsatellite markers with a maximum two-point LOD score of 3.42 (recombination fraction .05; P =6×10 −4 ; autosomal recessive mode of inheritance), whereas multipoint linkage calculations yielded a LOD score of 3.59. Haplotype analysis refined the genetic interval, positioning the RLS-predisposing gene in a 14.71-cM region between D12S1044 and D12S78. These findings represent the first mapping of a locus conferring susceptibility to RLS.
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Machado Joseph disease is not an allele of the spinocerebellar ataxia 2 locus
Human genetics, 1994Co-Authors: Elspeth C. Twist, Lindsay A. Farrer, Patrick Macleod, João Radvany, Susan Chamberlain, Roger N. Rosenberg, Guy A RouleauAbstract:Machado Joseph disease (MJD) is a progressive, spinocerebellar ataxia (SCA) with an autosomal dominant mode of inheritance and almost complete penetrance. Clinically, it is difficult to distinguish it from other autosomal dominantly inherited ataxias, and it has been suggested that MJD may be caused by an allelic variant of SCA. Exclusion of MJD from the SCA1 locus on Chromosome 6p has previously been demonstrated. However, following the recent assignment of a second locus for spinocerebellar ataxia (SCA2) to Chromosome 12q in a large Cuban kindred of Spanish origin, we have investigated linkage in MJD families using the two markers, D12S58 and PLA2, that flank this disease gene. The MJD locus was definitively excluded from an interval spanning approximately 70 cM, which includes these loci. These studies demonstrate that MJD and SCA2 are genetically distinct despite similarities in disease phenotype and ancestral origins of the patients. Thus, the as yet unmapped MJD locus represents a third SCA locus, providing further evidence for genetic heterogeneity within these disorders.
Ervin H. Epstein - One of the best experts on this subject based on the ideXlab platform.
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A novel mutation in the 1A domain of keratin 2e in ichthyosis bullosa of Siemens
The Journal of investigative dermatology, 1999Co-Authors: Meral J. Arin, Ervin H. Epstein, Lowell A. Goldsmith, Mary A. Longley, Glynis Scott, Joseph A. Rothnagel, Dennis R. RoopAbstract:Ichthyosis bullosa of Siemens (IBS) is a rare autosomal dominant skin disorder with clinical features similar to epidermolytic hyperkeratosis (EHK). Both diseases have been linked to the type II keratin cluster on Chromosome 12q. Hyperkeratosis and blister formation are relatively mild in IBS compared with EHK, and the lysis of keratinocytes is restricted to the upper spinous and granular layers of the epidermis of IBS patients, whereas in EHK lysis occurs in the lower spinous layer. Recently, mutations in the helix initiation and termination motifs of keratin 2e (K2e) have been described in IBS patients. The majority of the mutations reported to date lie in the 2B region. In this report, we have examined a large kindred in which the disease was originally diagnosed as EHK and mapped to the type II keratin cluster on Chromosome 12q. Molecular analysis revealed a novel amino acid substitution at the beginning of the conserved 1A region of the rod domain (I4N) of K2e, resulting from a T to A transversion in codon 188.
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Narrowing of the Darier Disease Gene Interval on Chromosome 12q
The Journal of investigative dermatology, 1998Co-Authors: Shigaku Ikeda, Lowell A. Goldsmith, Takako Shigihara, Hideoki Ogawa, Anne R. Haake, Renata Polakowska, Inna Roublevskaia, Paul Wakem, Ervin H. EpsteinAbstract:To the Editor:Darier disease (DD) is one of the classical Mendelian disorders ofthe skin whose cryptic pathogenesis has made it a prime candidatefor a ‘‘positional cloning’’ approach. These efforts first excluded thechromosomal sites of the genes known to be important in adhesionamong epidermal keratinocytes (Ikeda
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Linkage of the epidermolytic hyperkeratosis phenotype and the region of the type II keratin gene cluster on Chromosome 12.
Journal of Investigative Dermatology, 1992Co-Authors: Jeannette M. Bonifas, Lowell A. Goldsmith, Marisa A Chen, John W. Bare, Ming K Lee, Cathy A Slater, Ervin H. EpsteinAbstract:Bullous congenital ichthyosiform erythroderma (epidermolytic hyperkeratosis) is a severe, generalized, lifelong disease of the skin. As in epidermolysis bullosa simplex, intraepidermal blisters and clumping of keratin intermediate filaments are characteristic. We report here linkage of the inheritance of this disease to the region of Chromosome 12q containing the genes encoding type II keratins. This suggests that keratin gene mutations may underlie this complex hyperproliferative and hyperkeratotic phenotype.
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Regional assignment of the human keratin 5 (KRT5) gene to Chromosome 12q near D12S14 by PCR analysis of somatic cell hybrids and multicolor in situ hybridization.
Genomics, 1992Co-Authors: Jeannette M. Bonifas, John W. Bare, Eric Lynch, Roger V. Lebo, Ervin H. EpsteinAbstract:Keratin 5 is the major type II keratin of the basal cells of epidermis and of other stratified epithelia. With its type I partner, keratin 14, it constitutes a major fraction of the cytoskeleton of the basal cells. Because the inheritance of epidermolysis bullosa simplex, a disease of epidermal basal cell fragility, was mapped in one family to Chromosome 12q close to D12S14, we undertook to localize the gene for keratin 5. Polymerase chain reaction analysis of somatic cell hybrids mapped the keratin 5 gene to Chromosome 12, and multicolor fluorescence in situ hybridization localized it to 12q very near D12S14. This sublocalization exemplifies the utility of in situ physical localization in assessing the candidacy of genes thought to underlie inherited disorders.
Lowell A. Goldsmith - One of the best experts on this subject based on the ideXlab platform.
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Hot spot mutations in keratin 2e suggest a correlation between genotype and phenotype in patients with ichthyosis bullosa of Siemens.
Experimental dermatology, 2000Co-Authors: Yasushi Suga, Lowell A. Goldsmith, Meral J. Arin, Glynis Scott, Cynthia M. Magro, Lynn A. Baden, Howard P. Baden, Dennis R. RoopAbstract:Ichthyosis bullosa of Siemens (IBS) is a rare disorder of cornification characterized by blister formation in the upper suprabasal layers of the epidermis. Molecular analysis of IBS has identified mutations in the keratin 2e (K2e) gene, which is located in the type II keratin gene cluster on Chromosome 12q. We have studied two IBS families and have identified heterozygous point mutations in codon 493 of the K2e gene in both families. Whereas a non-conservative amino acid substitution at position 117 of the 2B region of K2e (E117K) was associated with a severe phenotype in family 1, family 2 showed mild clinical features as a result of a conservative substitution (E117D). These data suggest a phenotype-genotype correlation in these families.
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A novel mutation in the 1A domain of keratin 2e in ichthyosis bullosa of Siemens
The Journal of investigative dermatology, 1999Co-Authors: Meral J. Arin, Ervin H. Epstein, Lowell A. Goldsmith, Mary A. Longley, Glynis Scott, Joseph A. Rothnagel, Dennis R. RoopAbstract:Ichthyosis bullosa of Siemens (IBS) is a rare autosomal dominant skin disorder with clinical features similar to epidermolytic hyperkeratosis (EHK). Both diseases have been linked to the type II keratin cluster on Chromosome 12q. Hyperkeratosis and blister formation are relatively mild in IBS compared with EHK, and the lysis of keratinocytes is restricted to the upper spinous and granular layers of the epidermis of IBS patients, whereas in EHK lysis occurs in the lower spinous layer. Recently, mutations in the helix initiation and termination motifs of keratin 2e (K2e) have been described in IBS patients. The majority of the mutations reported to date lie in the 2B region. In this report, we have examined a large kindred in which the disease was originally diagnosed as EHK and mapped to the type II keratin cluster on Chromosome 12q. Molecular analysis revealed a novel amino acid substitution at the beginning of the conserved 1A region of the rod domain (I4N) of K2e, resulting from a T to A transversion in codon 188.
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Narrowing of the Darier Disease Gene Interval on Chromosome 12q
The Journal of investigative dermatology, 1998Co-Authors: Shigaku Ikeda, Lowell A. Goldsmith, Takako Shigihara, Hideoki Ogawa, Anne R. Haake, Renata Polakowska, Inna Roublevskaia, Paul Wakem, Ervin H. EpsteinAbstract:To the Editor:Darier disease (DD) is one of the classical Mendelian disorders ofthe skin whose cryptic pathogenesis has made it a prime candidatefor a ‘‘positional cloning’’ approach. These efforts first excluded thechromosomal sites of the genes known to be important in adhesionamong epidermal keratinocytes (Ikeda
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Linkage of the epidermolytic hyperkeratosis phenotype and the region of the type II keratin gene cluster on Chromosome 12.
Journal of Investigative Dermatology, 1992Co-Authors: Jeannette M. Bonifas, Lowell A. Goldsmith, Marisa A Chen, John W. Bare, Ming K Lee, Cathy A Slater, Ervin H. EpsteinAbstract:Bullous congenital ichthyosiform erythroderma (epidermolytic hyperkeratosis) is a severe, generalized, lifelong disease of the skin. As in epidermolysis bullosa simplex, intraepidermal blisters and clumping of keratin intermediate filaments are characteristic. We report here linkage of the inheritance of this disease to the region of Chromosome 12q containing the genes encoding type II keratins. This suggests that keratin gene mutations may underlie this complex hyperproliferative and hyperkeratotic phenotype.
Gustavo Turecki - One of the best experts on this subject based on the ideXlab platform.
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Restless Legs Syndrome Confirmation of Linkage to Chromosome 12q, Genetic Heterogeneity, and Evidence of Complexity
Archives of neurology, 2005Co-Authors: Alex Desautels, Gustavo Turecki, Jacques Montplaisir, Lan Xiong, Arthur S. Walters, Bruce L. Ehrenberg, Kateri Brisebois, Yves Gingras, William G. JohnsonAbstract:Background Genes are involved in the etiology of restless legs syndrome, a common sensorimotor disorder. Objectives To replicate and to further characterize our previously reported Chromosome 12q linkage results. Design Family linkage study. Setting and Participants A total of 276 individuals from 19 families have been examined using a selection of markers spanning the identified candidate interval on Chromosome 12q. Results Two-point analyses of individual pedigrees indicated that 5 kindreds were consistent with linkage to Chromosome 12q. When considering these 5 pedigrees along with the family in which linkage was originally reported, we observed a maximum 2-point logarithm-of-odds score of 5.67 (at θ = 0.10; for marker D12S1636 ; autosomal recessive) and a maximum multipoint logarithm-of-odds score of 8.84 between the interval defined by markers D12S326 and D12S304 . Furthermore, our results also suggest the presence of heterogeneity in restless legs syndrome as linkage was formally excluded across the region in 6 pedigrees. Interestingly, significantly higher periodic leg movements during sleep indices were observed for all probands with restless legs syndrome from linked families. Conclusions These results support the presence of a major restless legs syndrome–susceptibility locus on Chromosome 12q, which has been designated as RLS1 , and also suggest that at least one additional locus may be involved in the origin of this prevalent condition.
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Mutational analysis of neurotensin in familial restless legs syndrome
Movement disorders : official journal of the Movement Disorder Society, 2003Co-Authors: Alex Desautels, Gustavo Turecki, Jacques Montplaisir, Lan Xiong, Daniel Rochefort, Guy A RouleauAbstract:A susceptibility locus for restless legs syndrome (RLS) has been identified recently on Chromosome 12q. This region contains several transcribed genes including neurotensin (NTS), which, as an important modulator of the dopaminergic transmission, represents a strong functional and positional candidate in the context of RLS. In this study, NTS was evaluated for mutational analysis. A panel of 19 individuals from 4 families supporting linkage to 12q was investigated using a combined denaturing high-performance liquid chromatography (dHPLC) and direct sequencing method. Analysis of the NTS genomic sequence revealed 2 intronic polymorphisms and 1 variant located in the 5' untranslated region (UTR). None of the observed variants co-segregated with RLS and no disease-associated polymorphisms were detected in any of the analyzed families. Based on these results, it is unlikely that NTS is the gene responsible for RLS in Chromosome 12-linked families.
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Reply to Kock et al.
The American Journal of Human Genetics, 2002Co-Authors: Alex Desautels, Gustavo Turecki, Jacques Montplaisir, G. A. RouleauAbstract:To the Editor:In their study, Kock et al. (2002xMode of inheritance and susceptibility locus for restless legs syndrome, on Chromosome 12q. Kock, N, Culjkovic, B, Maniak, S, Schilling, K, Muller, B, Zuhlke, C, Ozelius, L, Klein, C, Pramstaller, PP, and Kramer, PL. Am J Hum Genet. 2002; 71: 205–208Abstract | Full Text | Full Text PDF | PubMed | Scopus (32)See all References2002 [in this issue]) investigated two families from South Tyrol, to test for linkage with a restless legs syndrome (RLS)–susceptibility locus, on Chromosome 12q, that was recently identified by our group (Desautels et al. 2001xIdentification of a major susceptibility locus for restless legs syndrome on Chromosome 12q. Desautels, A, Turecki, G, Montplaisir, J, Sequeira, A, Verner, A, and Rouleau, GA. Am J Hum Genet. 2001; 69: 1266–1270Abstract | Full Text | Full Text PDF | PubMed | Scopus (214)See all References2001). They genotyped a total of 51 subjects by use of four markers spanning a 17-cM interval on the candidate region. Assuming both a dominant and a recessive mode of inheritance, Kock et al. failed to replicate our reported linkage on Chromosome 12q in the families that they studied. In addition, aiming to reproduce our original results, they subsequently analyzed the same family that we studied by use of our marker data and the published recessive model, assuming a phenocopy rate of 80%. Being unable to replicate our findings by use of our own material, Kock et al. have raised some concerns regarding the recessive model described in our article.Unfortunately, the published version of our original article reporting linkage between RLS and a locus on Chromosome 12q (Desautels et al. 2001xIdentification of a major susceptibility locus for restless legs syndrome on Chromosome 12q. Desautels, A, Turecki, G, Montplaisir, J, Sequeira, A, Verner, A, and Rouleau, GA. Am J Hum Genet. 2001; 69: 1266–1270Abstract | Full Text | Full Text PDF | PubMed | Scopus (214)See all References2001) contained an error. Indeed, the information presented for the penetrance values and phenocopy rates in the published table (p. 1267) does not correspond to the values used in our analyses. The genetic models used by our group were based on realistic assumptions, which are listed below, in the rectified version of the table (table 1table 1; for the recessive model, the disease-allele frequency was set at 0.25 with a reduced penetrance of 0.8 and an estimated phenocopy rate of 0.005). The error involves only the presentation of the table, not the parametric analyses per se. Therefore, this will clarify the issue pertaining to our model raised by Kock et al., since their criticisms were based on misinterpretations induced by this unfortunate error.Table 1Genetic Models Used in the Parametric AnalysisAllele FrequencyPenetranceModel of Inheritancepqf1f2f0Dominant 1.99.01.9.90Dominant 2.95.05.5.5.005Recessive.75.25.8.005.005Note.—θ Between males and females was considered to be equal.The nonreplication of our positive linkage in two South Tyrolean families' results raises the hypothesis that genetic heterogeneity is present. Accordingly, since the publication of the original study, additional families have been recruited and investigated for the candidate interval. Although linkage to Chromosome 12q has been confirmed in some kindreds, our analyses indicate that a number of families are definitely not linked to this region, further supporting the heterogeneity hypothesis (A. Desautels, G. Turecki, J. Montplaisir, A. S. Walters, B. L. Ehrenberg, K. Brisebois, A. K. Desautels, W. G. Johnson, E. Lugaresi, G. Coccagna, D. L. Picchietti, A. Lazzarini, Y. Gingras, and G. A. Rouleau, unpublished data). Taken together, these data suggest that other putative loci, besides the locus on Chromosome 12q that has recently been identified by our group, could be involved in the etiology of this common sleep disorder.
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identification of a major susceptibility locus for restless legs syndrome on Chromosome 12q
American Journal of Human Genetics, 2001Co-Authors: Alex Desautels, Gustavo Turecki, Jacques Y Montplaisir, Adolfo Sequeira, Andrei Verner, Guy A RouleauAbstract:Restless legs syndrome (RLS) is a neurological disorder characterized by leg paresthesia associated with an irresistible urge to move that often interferes with nocturnal sleep, leading to chronic sleep deprivation. To map genes that may play a role in the vulnerability to RLS, a genomewide scan was conducted in a large French-Canadian family. Significant linkage was established on Chromosome 12q, for a series of adjacent microsatellite markers with a maximum two-point LOD score of 3.42 (recombination fraction .05; P =6×10 −4 ; autosomal recessive mode of inheritance), whereas multipoint linkage calculations yielded a LOD score of 3.59. Haplotype analysis refined the genetic interval, positioning the RLS-predisposing gene in a 14.71-cM region between D12S1044 and D12S78. These findings represent the first mapping of a locus conferring susceptibility to RLS.
Alex Desautels - One of the best experts on this subject based on the ideXlab platform.
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Genetic association studies of neurotensin gene and restless legs syndrome in French Canadians
Sleep medicine, 2007Co-Authors: Lan Xiong, Jacques Montplaisir, Alex Desautels, Anastasia Levchenko, Jean-baptiste Rivière, Pascale Thibodeau, Judith St-onge, Claudia Gaspar, Paul Lespérance, Sylvain ChouinardAbstract:Abstract Background and purpose The neurotensin gene (NTS), a known dopamine modulator, is located within the candidate region for the first genetic locus of restless legs syndrome (RLS1) on Chromosome 12q. Though no causative mutation was found in selected patients in a previous mutation analysis, the involvement of NTS in RLS cannot be completely excluded as a potential positional and functional candidate gene. The purpose of the current study is to further explore the NTS gene for potential functional variant(s) in its entire genomic and potential regulatory regions and their possible association with RLS symptoms. Methods and subjects We resequenced the coding regions and sequenced all the intronic and potential regulatory regions of the NTS gene in additional patients and controls. We carried out full scale gene-based case-control and family-based genetic association studies using the sequence variants detected during mutational analysis. Results No coding or variants in regulatory and intronic regions compatible with a deleterious mutation were detected. Seven polymorphisms with elevated allele frequencies in the Caucasian population did not show association with RLS in two independent case-control groups and 110 RLS families. Conclusion The NTS gene on Chromosome 12q is most unlikely to play a direct role in RLS etiology.
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Mutational analysis of neurotensin in familial restless legs syndrome
Movement disorders : official journal of the Movement Disorder Society, 2003Co-Authors: Alex Desautels, Gustavo Turecki, Jacques Montplaisir, Lan Xiong, Daniel Rochefort, Guy A RouleauAbstract:A susceptibility locus for restless legs syndrome (RLS) has been identified recently on Chromosome 12q. This region contains several transcribed genes including neurotensin (NTS), which, as an important modulator of the dopaminergic transmission, represents a strong functional and positional candidate in the context of RLS. In this study, NTS was evaluated for mutational analysis. A panel of 19 individuals from 4 families supporting linkage to 12q was investigated using a combined denaturing high-performance liquid chromatography (dHPLC) and direct sequencing method. Analysis of the NTS genomic sequence revealed 2 intronic polymorphisms and 1 variant located in the 5' untranslated region (UTR). None of the observed variants co-segregated with RLS and no disease-associated polymorphisms were detected in any of the analyzed families. Based on these results, it is unlikely that NTS is the gene responsible for RLS in Chromosome 12-linked families.
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Reply to Kock et al.
The American Journal of Human Genetics, 2002Co-Authors: Alex Desautels, Gustavo Turecki, Jacques Montplaisir, G. A. RouleauAbstract:To the Editor:In their study, Kock et al. (2002xMode of inheritance and susceptibility locus for restless legs syndrome, on Chromosome 12q. Kock, N, Culjkovic, B, Maniak, S, Schilling, K, Muller, B, Zuhlke, C, Ozelius, L, Klein, C, Pramstaller, PP, and Kramer, PL. Am J Hum Genet. 2002; 71: 205–208Abstract | Full Text | Full Text PDF | PubMed | Scopus (32)See all References2002 [in this issue]) investigated two families from South Tyrol, to test for linkage with a restless legs syndrome (RLS)–susceptibility locus, on Chromosome 12q, that was recently identified by our group (Desautels et al. 2001xIdentification of a major susceptibility locus for restless legs syndrome on Chromosome 12q. Desautels, A, Turecki, G, Montplaisir, J, Sequeira, A, Verner, A, and Rouleau, GA. Am J Hum Genet. 2001; 69: 1266–1270Abstract | Full Text | Full Text PDF | PubMed | Scopus (214)See all References2001). They genotyped a total of 51 subjects by use of four markers spanning a 17-cM interval on the candidate region. Assuming both a dominant and a recessive mode of inheritance, Kock et al. failed to replicate our reported linkage on Chromosome 12q in the families that they studied. In addition, aiming to reproduce our original results, they subsequently analyzed the same family that we studied by use of our marker data and the published recessive model, assuming a phenocopy rate of 80%. Being unable to replicate our findings by use of our own material, Kock et al. have raised some concerns regarding the recessive model described in our article.Unfortunately, the published version of our original article reporting linkage between RLS and a locus on Chromosome 12q (Desautels et al. 2001xIdentification of a major susceptibility locus for restless legs syndrome on Chromosome 12q. Desautels, A, Turecki, G, Montplaisir, J, Sequeira, A, Verner, A, and Rouleau, GA. Am J Hum Genet. 2001; 69: 1266–1270Abstract | Full Text | Full Text PDF | PubMed | Scopus (214)See all References2001) contained an error. Indeed, the information presented for the penetrance values and phenocopy rates in the published table (p. 1267) does not correspond to the values used in our analyses. The genetic models used by our group were based on realistic assumptions, which are listed below, in the rectified version of the table (table 1table 1; for the recessive model, the disease-allele frequency was set at 0.25 with a reduced penetrance of 0.8 and an estimated phenocopy rate of 0.005). The error involves only the presentation of the table, not the parametric analyses per se. Therefore, this will clarify the issue pertaining to our model raised by Kock et al., since their criticisms were based on misinterpretations induced by this unfortunate error.Table 1Genetic Models Used in the Parametric AnalysisAllele FrequencyPenetranceModel of Inheritancepqf1f2f0Dominant 1.99.01.9.90Dominant 2.95.05.5.5.005Recessive.75.25.8.005.005Note.—θ Between males and females was considered to be equal.The nonreplication of our positive linkage in two South Tyrolean families' results raises the hypothesis that genetic heterogeneity is present. Accordingly, since the publication of the original study, additional families have been recruited and investigated for the candidate interval. Although linkage to Chromosome 12q has been confirmed in some kindreds, our analyses indicate that a number of families are definitely not linked to this region, further supporting the heterogeneity hypothesis (A. Desautels, G. Turecki, J. Montplaisir, A. S. Walters, B. L. Ehrenberg, K. Brisebois, A. K. Desautels, W. G. Johnson, E. Lugaresi, G. Coccagna, D. L. Picchietti, A. Lazzarini, Y. Gingras, and G. A. Rouleau, unpublished data). Taken together, these data suggest that other putative loci, besides the locus on Chromosome 12q that has recently been identified by our group, could be involved in the etiology of this common sleep disorder.
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identification of a major susceptibility locus for restless legs syndrome on Chromosome 12q
American Journal of Human Genetics, 2001Co-Authors: Alex Desautels, Gustavo Turecki, Jacques Y Montplaisir, Adolfo Sequeira, Andrei Verner, Guy A RouleauAbstract:Restless legs syndrome (RLS) is a neurological disorder characterized by leg paresthesia associated with an irresistible urge to move that often interferes with nocturnal sleep, leading to chronic sleep deprivation. To map genes that may play a role in the vulnerability to RLS, a genomewide scan was conducted in a large French-Canadian family. Significant linkage was established on Chromosome 12q, for a series of adjacent microsatellite markers with a maximum two-point LOD score of 3.42 (recombination fraction .05; P =6×10 −4 ; autosomal recessive mode of inheritance), whereas multipoint linkage calculations yielded a LOD score of 3.59. Haplotype analysis refined the genetic interval, positioning the RLS-predisposing gene in a 14.71-cM region between D12S1044 and D12S78. These findings represent the first mapping of a locus conferring susceptibility to RLS.