Dépouillements

Deep exon resequencing of DLGAP2 as a candidate gene of autism spectrum disorders / Wei-Hsien CHIEN in Molecular Autism, (August 2013)  

Public ISBD [article]  inMolecular Autism > (August 2013) . - 23 p. Titre : Deep exon resequencing of DLGAP2 as a candidate gene of autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Wei-Hsien CHIEN, Auteur ; Susan Shur-Fen GAU, Auteur ; Hsiao-Mei LIAO, Auteur ; Yen-Nan CHIU, Auteur ; Yu-Yu WU, Auteur ; Yu-Shu HUANG, Auteur ; Wen-Che TSAI, Auteur ; Ho-Min TSAI, Auteur ; Chia-Hsiang CHEN, Auteur Année de publication : 2013 Article en page(s) : 23 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background We recently reported a terminal deletion of approximately 2.4 Mb at chromosome 8p23.2-pter in a boy with autism. The deleted region contained the DLGAP2 gene that encodes the neuronal post-synaptic density protein, discs, large (Drosophila) homolog-associated protein 2. The study aimed to investigate whether DLGAP2 is genetically associated with autism spectrum disorders (ASD) in general. Methods We re-sequenced all the exons of DLGPA2 in 515 patients with ASD and 596 control subjects from Taiwan. We also conducted bioinformatic analysis and family study of variants identified in this study. Results We detected nine common single nucleotide polymorphisms (SNPs) and sixteen novel missense rare variants in this sample. We found that AA homozygotes of rs2906569 (minor allele G, alternate allele A) at intron 1 (P = 0.003) and CC homozygotes of rs2301963 (minor allele A, alternate allele C) at exon 3 (P = 0.0003) were significantly over-represented in the patient group compared to the controls. We also found no differences in the combined frequency of rare missense variants between the two groups. Some of these rare variants were predicted to have an impact on the function of DLGAP2 using informatics analysis, and the family study revealed most of the rare missense mutations in patients were inherited from their unaffected parents. Conclusions We detected some common and rare genetic variants of DLGAP2 that might have implication in the pathogenesis of ASD, but they alone may not be sufficient to lead to clinical phenotypes. We suggest that further genetic or environmental factors in affected patients may be present and determine the clinical manifestations. Trial registration ClinicalTrial.gov, NCT00494754 En ligne : http://dx.doi.org/10.1186/2040-2392-4-26 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211 [article] Deep exon resequencing of DLGAP2 as a candidate gene of autism spectrum disorders [Texte imprimé et/ou numérique] / Wei-Hsien CHIEN, Auteur ; Susan Shur-Fen GAU, Auteur ; Hsiao-Mei LIAO, Auteur ; Yen-Nan CHIU, Auteur ; Yu-Yu WU, Auteur ; Yu-Shu HUANG, Auteur ; Wen-Che TSAI, Auteur ; Ho-Min TSAI, Auteur ; Chia-Hsiang CHEN, Auteur . - 2013 . - 23 p. Langues : Anglais (eng) in Molecular Autism > (August 2013) . - 23 p. Index. décimale : PER Périodiques Résumé : Background We recently reported a terminal deletion of approximately 2.4 Mb at chromosome 8p23.2-pter in a boy with autism. The deleted region contained the DLGAP2 gene that encodes the neuronal post-synaptic density protein, discs, large (Drosophila) homolog-associated protein 2. The study aimed to investigate whether DLGAP2 is genetically associated with autism spectrum disorders (ASD) in general. Methods We re-sequenced all the exons of DLGPA2 in 515 patients with ASD and 596 control subjects from Taiwan. We also conducted bioinformatic analysis and family study of variants identified in this study. Results We detected nine common single nucleotide polymorphisms (SNPs) and sixteen novel missense rare variants in this sample. We found that AA homozygotes of rs2906569 (minor allele G, alternate allele A) at intron 1 (P = 0.003) and CC homozygotes of rs2301963 (minor allele A, alternate allele C) at exon 3 (P = 0.0003) were significantly over-represented in the patient group compared to the controls. We also found no differences in the combined frequency of rare missense variants between the two groups. Some of these rare variants were predicted to have an impact on the function of DLGAP2 using informatics analysis, and the family study revealed most of the rare missense mutations in patients were inherited from their unaffected parents. Conclusions We detected some common and rare genetic variants of DLGAP2 that might have implication in the pathogenesis of ASD, but they alone may not be sufficient to lead to clinical phenotypes. We suggest that further genetic or environmental factors in affected patients may be present and determine the clinical manifestations. Trial registration ClinicalTrial.gov, NCT00494754 En ligne : http://dx.doi.org/10.1186/2040-2392-4-26 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211

Do girls with anorexia nervosa have elevated autistic traits? / Simon BARON-COHEN in Molecular Autism, (August 2013)  

Public ISBD [article]  inMolecular Autism > (August 2013) . - 8 p. Titre : Do girls with anorexia nervosa have elevated autistic traits? Type de document : Texte imprimé et/ou numérique Auteurs : Simon BARON-COHEN, Auteur ; Tony JAFFA, Auteur ; Sarah DAVIES, Auteur ; Bonnie AUYEUNG, Auteur ; Carrie ALLISON, Auteur ; Sally WHEELWRIGHT, Auteur Année de publication : 2013 Article en page(s) : 8 p. Langues : Anglais (eng) Mots-clés : Autistic traits  Anorexia  Autism spectrum conditions  Broader autism phenotype Index. décimale : PER Périodiques Résumé : Background Patients with anorexia may have elevated autistic traits. In this study, we tested test whether patients with anorexia nervosa (anorexia) have an elevated score on a dimensional measure of autistic traits, the Autism Spectrum Quotient (AQ), as well as on trait measures relevant to the autism spectrum: the Empathy Quotient (EQ), and the Systemizing Quotient (SQ). Methods Two groups were tested: (1) female adolescents with anorexia: n?=?66, aged 12 to 18 years; and (2) female adolescents without anorexia: n =1,609, aged 12 to 18 years. Both groups were tested using the AQ, EQ, and SQ, via the parent-report adolescent versions for patients aged 12 to 15 years old, and the self-report adult versions for patients aged over 16 years. Results As predicted, the patients with anorexia had a higher AQ and SQ. Their EQ score was reduced, but only for the parent-report version in the younger age group. Using EQ-SQ scores to calculate ‘cognitive types’, patients with anorexia were more likely to show the Type S profile (systemizing (S) better than empathy (E)), compared with typical females. Conclusions Females with anorexia have elevated autistic traits. Clinicians should consider if a focus on autistic traits might be helpful in the assessment and treatment of anorexia. Future research needs to establish if these results reflect traits or states associated with anorexia. En ligne : http://dx.doi.org/10.1186/2040-2392-4-24 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211 [article] Do girls with anorexia nervosa have elevated autistic traits? [Texte imprimé et/ou numérique] / Simon BARON-COHEN, Auteur ; Tony JAFFA, Auteur ; Sarah DAVIES, Auteur ; Bonnie AUYEUNG, Auteur ; Carrie ALLISON, Auteur ; Sally WHEELWRIGHT, Auteur . - 2013 . - 8 p. Langues : Anglais (eng) in Molecular Autism > (August 2013) . - 8 p. Mots-clés : Autistic traits  Anorexia  Autism spectrum conditions  Broader autism phenotype Index. décimale : PER Périodiques Résumé : Background Patients with anorexia may have elevated autistic traits. In this study, we tested test whether patients with anorexia nervosa (anorexia) have an elevated score on a dimensional measure of autistic traits, the Autism Spectrum Quotient (AQ), as well as on trait measures relevant to the autism spectrum: the Empathy Quotient (EQ), and the Systemizing Quotient (SQ). Methods Two groups were tested: (1) female adolescents with anorexia: n?=?66, aged 12 to 18 years; and (2) female adolescents without anorexia: n =1,609, aged 12 to 18 years. Both groups were tested using the AQ, EQ, and SQ, via the parent-report adolescent versions for patients aged 12 to 15 years old, and the self-report adult versions for patients aged over 16 years. Results As predicted, the patients with anorexia had a higher AQ and SQ. Their EQ score was reduced, but only for the parent-report version in the younger age group. Using EQ-SQ scores to calculate ‘cognitive types’, patients with anorexia were more likely to show the Type S profile (systemizing (S) better than empathy (E)), compared with typical females. Conclusions Females with anorexia have elevated autistic traits. Clinicians should consider if a focus on autistic traits might be helpful in the assessment and treatment of anorexia. Future research needs to establish if these results reflect traits or states associated with anorexia. En ligne : http://dx.doi.org/10.1186/2040-2392-4-24 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211

Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders / Jordan M. RAMSEY in Molecular Autism, (August 2013)  

Public ISBD [article]  inMolecular Autism > (August 2013) . - 18 p. Titre : Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Jordan M. RAMSEY, Auteur ; Paul C. GUEST, Auteur ; Jantine A.C. BROEK, Auteur ; Jeffrey GLENNON, Auteur ; Nanda N. ROMMELSE, Auteur ; Barbara FRANKE, Auteur ; Hassan RAHMOUNE, Auteur ; Jan K. BUITELAAR, Auteur ; Sabine BAHN, Auteur Année de publication : 2013 Article en page(s) : 18 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background Autism spectrum disorders (ASDs) are neurodevelopmental conditions with symptoms manifesting before the age of 3, generally persisting throughout life and affecting social development and communication. Here, we have investigated changes in protein biomarkers in blood during childhood and adolescent development. Methods We carried out a multiplex immunoassay profiling analysis of serum samples from 37 individuals with a diagnosis of ASD and their matched, non-affected siblings, aged between 4 and 18 years, to identify molecular pathways affected over the course of ASDs. Results This analysis revealed age-dependent differences in the levels of 12 proteins involved in inflammation, growth and hormonal signaling. Conclusions These deviations in age-related molecular trajectories provide further insight into the progression and pathophysiology of the disorder and, if replicated, may contribute to better classification of ASD individuals, as well as to improved treatment and prognosis. The results also underline the importance of stratifying and analyzing samples by age, especially in ASD and potentially other developmental disorders. En ligne : http://dx.doi.org/10.1186/2040-2392-4-27 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211 [article] Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders [Texte imprimé et/ou numérique] / Jordan M. RAMSEY, Auteur ; Paul C. GUEST, Auteur ; Jantine A.C. BROEK, Auteur ; Jeffrey GLENNON, Auteur ; Nanda N. ROMMELSE, Auteur ; Barbara FRANKE, Auteur ; Hassan RAHMOUNE, Auteur ; Jan K. BUITELAAR, Auteur ; Sabine BAHN, Auteur . - 2013 . - 18 p. Langues : Anglais (eng) in Molecular Autism > (August 2013) . - 18 p. Index. décimale : PER Périodiques Résumé : Background Autism spectrum disorders (ASDs) are neurodevelopmental conditions with symptoms manifesting before the age of 3, generally persisting throughout life and affecting social development and communication. Here, we have investigated changes in protein biomarkers in blood during childhood and adolescent development. Methods We carried out a multiplex immunoassay profiling analysis of serum samples from 37 individuals with a diagnosis of ASD and their matched, non-affected siblings, aged between 4 and 18 years, to identify molecular pathways affected over the course of ASDs. Results This analysis revealed age-dependent differences in the levels of 12 proteins involved in inflammation, growth and hormonal signaling. Conclusions These deviations in age-related molecular trajectories provide further insight into the progression and pathophysiology of the disorder and, if replicated, may contribute to better classification of ASD individuals, as well as to improved treatment and prognosis. The results also underline the importance of stratifying and analyzing samples by age, especially in ASD and potentially other developmental disorders. En ligne : http://dx.doi.org/10.1186/2040-2392-4-27 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211

Presence of autism, hyperserotonemia, and severe expressive language impairment in Williams-Beuren syndrome / Sylvie TORDJMAN in Molecular Autism, (August 2013)  

Public ISBD [article]  inMolecular Autism > (August 2013) Titre : Presence of autism, hyperserotonemia, and severe expressive language impairment in Williams-Beuren syndrome Type de document : Texte imprimé et/ou numérique Auteurs : Sylvie TORDJMAN, Auteur ; George M. ANDERSON, Auteur ; David COHEN, Auteur ; Solenn KERMARREC, Auteur ; Michèle CARLIER, Auteur ; Yvan TOUITOU, Auteur ; Pascale SAUGIER-VEBER, Auteur ; Celine LAGNEAUX, Auteur ; Claire CHEVREUIL, Auteur ; Alain VERLOES, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND:Deletion of the Williams-Beuren syndrome (WBS) critical region (WBSCR), at 7q11.23, causes a developmental disorder commonly characterized by hypersociability and excessive talkativeness and often considered the opposite behavioral phenotype to autism. Duplication of the WBSCR leads to severe delay in expressive language. Gene-dosage effects on language development at 7q11.23 have been hypothesized.METHODS:Molecular characterization of the WBSCR was performed by fluorescence in situ hybridization and high-resolution single-nucleotide polymorphism array in two individuals with severe autism enrolled in a genetic study of autism who showed typical WBS facial dysmorphism on systematic clinical genetic examination. The serotonin transporter promoter polymorphism (5-HTTLPR, locus SLC6A4) was genotyped. Platelet serotonin levels and urinary 6-sulfatoxymelatonin excretion were measured. Behavioral and cognitive phenotypes were examined.RESULTS:The two patients had common WBSCR deletions between proximal and medial low copy repeat clusters, met diagnostic criteria for autism and displayed severe impairment in communication, including a total absence of expressive speech. Both patients carried the 5-HTTLPR ss genotype and exhibited platelet hyperserotonemia and low melatonin production.CONCLUSIONS:Our observations indicate that behaviors and neurochemical phenotypes typically associated with autism can occur in patients with common WBSCR deletions. The results raise intriguing questions about phenotypic heterogeneity in WBS and regarding genetic and/or environmental factors interacting with specific genes at 7q11.23 sensitive to dosage alterations that can influence the development of social communication skills. Thus, the influence of WBSCR genes on social communication expression might be dramatically modified by other genes, such as 5-HTTLPR, known to influence the severity of social communication impairments in autism, or by environmental factors, such as hyperserotonemia, given that hyperserotonemia is found in WBS associated with autism but not in WBS without autism. In this regard, WBS provides a potentially fruitful model with which to develop integrated genetic, cognitive, behavioral and neurochemical approaches to study genotype-phenotype correlations, possible gene-environment interactions and genetic background effects. The results underscore the importance of considering careful clinical and molecular genetic examination of individuals diagnosed with autism. En ligne : http://dx.doi.org/10.1186/2040-2392-4-29 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Presence of autism, hyperserotonemia, and severe expressive language impairment in Williams-Beuren syndrome [Texte imprimé et/ou numérique] / Sylvie TORDJMAN, Auteur ; George M. ANDERSON, Auteur ; David COHEN, Auteur ; Solenn KERMARREC, Auteur ; Michèle CARLIER, Auteur ; Yvan TOUITOU, Auteur ; Pascale SAUGIER-VEBER, Auteur ; Celine LAGNEAUX, Auteur ; Claire CHEVREUIL, Auteur ; Alain VERLOES, Auteur. Langues : Anglais (eng) in Molecular Autism > (August 2013) Index. décimale : PER Périodiques Résumé : BACKGROUND:Deletion of the Williams-Beuren syndrome (WBS) critical region (WBSCR), at 7q11.23, causes a developmental disorder commonly characterized by hypersociability and excessive talkativeness and often considered the opposite behavioral phenotype to autism. Duplication of the WBSCR leads to severe delay in expressive language. Gene-dosage effects on language development at 7q11.23 have been hypothesized.METHODS:Molecular characterization of the WBSCR was performed by fluorescence in situ hybridization and high-resolution single-nucleotide polymorphism array in two individuals with severe autism enrolled in a genetic study of autism who showed typical WBS facial dysmorphism on systematic clinical genetic examination. The serotonin transporter promoter polymorphism (5-HTTLPR, locus SLC6A4) was genotyped. Platelet serotonin levels and urinary 6-sulfatoxymelatonin excretion were measured. Behavioral and cognitive phenotypes were examined.RESULTS:The two patients had common WBSCR deletions between proximal and medial low copy repeat clusters, met diagnostic criteria for autism and displayed severe impairment in communication, including a total absence of expressive speech. Both patients carried the 5-HTTLPR ss genotype and exhibited platelet hyperserotonemia and low melatonin production.CONCLUSIONS:Our observations indicate that behaviors and neurochemical phenotypes typically associated with autism can occur in patients with common WBSCR deletions. The results raise intriguing questions about phenotypic heterogeneity in WBS and regarding genetic and/or environmental factors interacting with specific genes at 7q11.23 sensitive to dosage alterations that can influence the development of social communication skills. Thus, the influence of WBSCR genes on social communication expression might be dramatically modified by other genes, such as 5-HTTLPR, known to influence the severity of social communication impairments in autism, or by environmental factors, such as hyperserotonemia, given that hyperserotonemia is found in WBS associated with autism but not in WBS without autism. In this regard, WBS provides a potentially fruitful model with which to develop integrated genetic, cognitive, behavioral and neurochemical approaches to study genotype-phenotype correlations, possible gene-environment interactions and genetic background effects. The results underscore the importance of considering careful clinical and molecular genetic examination of individuals diagnosed with autism. En ligne : http://dx.doi.org/10.1186/2040-2392-4-29 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227

Rare coding variants of the adenosine A3 receptor are increased in autism: on the trail of the serotonin transporter regulome / Nicholas G. CAMPBELL in Molecular Autism, (August 2013)  

Public ISBD [article]  inMolecular Autism > (August 2013) Titre : Rare coding variants of the adenosine A3 receptor are increased in autism: on the trail of the serotonin transporter regulome Type de document : Texte imprimé et/ou numérique Auteurs : Nicholas G. CAMPBELL, Auteur ; Chong-Bin ZHU, Auteur ; Kathryn LINDLER, Auteur ; Brian YASPAN, Auteur ; Emily KISTNER-GRIFFIN, Auteur ; NIH ARRA CONSORTIUM,, Auteur ; William HEWLETT, Auteur ; Christopher TATE, Auteur ; Randy BLAKELY, Auteur ; James SUTCLIFFE, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND:Rare genetic variation is an important class of autism spectrum disorder (ASD) risk factors and can implicate biological networks for investigation. Altered serotonin (5-HT) signaling has been implicated in ASD, and we and others have discovered multiple, rare, ASD-associated variants in the 5-HT transporter (SERT) gene leading to elevated 5-HT re-uptake and perturbed regulation. We hypothesized that loci encoding SERT regulators harbor variants that impact SERT function and/or regulation and therefore could contribute to ASD risk. The adenosine A3 receptor (A3AR) regulates SERT via protein kinase G (PKG) and other signaling pathways leading to enhanced SERT surface expression and catalytic activity.METHODS:To test our hypothesis, we asked whether rare variants in the A3AR gene (ADORA3) were increased in ASD cases vs. controls. Discovery sequencing in a case-control sample and subsequent analysis of comparison exome sequence data were conducted. We evaluated the functional impact of two variants from the discovery sample on A3AR signaling and SERT activity.RESULTS:Sequencing discovery showed an increase of rare coding variants in cases vs. controls (P=0.013). While comparison exome sequence data did not show a significant enrichment (P=0.071), combined analysis strengthened evidence for association (P=0.0025). Two variants discovered in ASD cases (Leu90Val and Val171Ile) lie in or near the ligand-binding pocket, and Leu90Val was enriched individually in cases (P=0.040). In vitro analysis of cells expressing Val90-A3AR revealed elevated basal cGMP levels compared with the wildtype receptor. Additionally, a specific A3AR agonist increased cGMP levels across the full time course studied in Val90-A3AR cells, compared to wildtype receptor. In Val90-A3AR/SERT co-transfections, agonist stimulation elevated SERT activity over the wildtype receptor with delayed 5-HT uptake activity recovery. In contrast, Ile171-A3AR was unable to support agonist stimulation of SERT. Although both Val90 and Ile171 were present in greater numbers in these ASD cases, segregation analysis in families showed incomplete penetrance, consistent with other rare ASD risk alleles.CONCLUSIONS:Our results validate the hypothesis that the SERT regulatory network harbors rare, functional variants that impact SERT activity and regulation in ASD, and encourages further investigation of this network for other variation that may impact ASD risk. En ligne : http://dx.doi.org/10.1186/2040-2392-4-28 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Rare coding variants of the adenosine A3 receptor are increased in autism: on the trail of the serotonin transporter regulome [Texte imprimé et/ou numérique] / Nicholas G. CAMPBELL, Auteur ; Chong-Bin ZHU, Auteur ; Kathryn LINDLER, Auteur ; Brian YASPAN, Auteur ; Emily KISTNER-GRIFFIN, Auteur ; NIH ARRA CONSORTIUM,, Auteur ; William HEWLETT, Auteur ; Christopher TATE, Auteur ; Randy BLAKELY, Auteur ; James SUTCLIFFE, Auteur. Langues : Anglais (eng) in Molecular Autism > (August 2013) Index. décimale : PER Périodiques Résumé : BACKGROUND:Rare genetic variation is an important class of autism spectrum disorder (ASD) risk factors and can implicate biological networks for investigation. Altered serotonin (5-HT) signaling has been implicated in ASD, and we and others have discovered multiple, rare, ASD-associated variants in the 5-HT transporter (SERT) gene leading to elevated 5-HT re-uptake and perturbed regulation. We hypothesized that loci encoding SERT regulators harbor variants that impact SERT function and/or regulation and therefore could contribute to ASD risk. The adenosine A3 receptor (A3AR) regulates SERT via protein kinase G (PKG) and other signaling pathways leading to enhanced SERT surface expression and catalytic activity.METHODS:To test our hypothesis, we asked whether rare variants in the A3AR gene (ADORA3) were increased in ASD cases vs. controls. Discovery sequencing in a case-control sample and subsequent analysis of comparison exome sequence data were conducted. We evaluated the functional impact of two variants from the discovery sample on A3AR signaling and SERT activity.RESULTS:Sequencing discovery showed an increase of rare coding variants in cases vs. controls (P=0.013). While comparison exome sequence data did not show a significant enrichment (P=0.071), combined analysis strengthened evidence for association (P=0.0025). Two variants discovered in ASD cases (Leu90Val and Val171Ile) lie in or near the ligand-binding pocket, and Leu90Val was enriched individually in cases (P=0.040). In vitro analysis of cells expressing Val90-A3AR revealed elevated basal cGMP levels compared with the wildtype receptor. Additionally, a specific A3AR agonist increased cGMP levels across the full time course studied in Val90-A3AR cells, compared to wildtype receptor. In Val90-A3AR/SERT co-transfections, agonist stimulation elevated SERT activity over the wildtype receptor with delayed 5-HT uptake activity recovery. In contrast, Ile171-A3AR was unable to support agonist stimulation of SERT. Although both Val90 and Ile171 were present in greater numbers in these ASD cases, segregation analysis in families showed incomplete penetrance, consistent with other rare ASD risk alleles.CONCLUSIONS:Our results validate the hypothesis that the SERT regulatory network harbors rare, functional variants that impact SERT activity and regulation in ASD, and encourages further investigation of this network for other variation that may impact ASD risk. En ligne : http://dx.doi.org/10.1186/2040-2392-4-28 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227