Pernille Axél Gregersen, Anna Hammarsjö, Lise Graversen, Nis Brix, Hillevi Lindelöf, Uffe Birk Jensen, Stense Farholt, Sune Rubak, Jesper Bjerre, Serena G Piticchio, Thorkild Terkelsen, Gen Nishimura, Michel Bach Hellfritzsch, Giedre Grigelioniene
{"title":"Compound heterozygosity for two variants in BMP5 in human skeletal dysostosis with atrioventricular septal defect.","authors":"Pernille Axél Gregersen, Anna Hammarsjö, Lise Graversen, Nis Brix, Hillevi Lindelöf, Uffe Birk Jensen, Stense Farholt, Sune Rubak, Jesper Bjerre, Serena G Piticchio, Thorkild Terkelsen, Gen Nishimura, Michel Bach Hellfritzsch, Giedre Grigelioniene","doi":"10.1111/cge.14616","DOIUrl":"https://doi.org/10.1111/cge.14616","url":null,"abstract":"<p><p>The growth and development of the skeleton is regulated by bone morphogenetic proteins of which several are linked to genetic skeletal disorders. So far, no human skeletal malformations have been associated with variants in BMP5. Here, we report a patient with biallelic loss of function variants in BMP5 and a syndromic phenotype including skeletal dysostosis, dysmorphic features, hypermobility, laryngo-tracheo-bronchomalacia and atrioventricular septal defect. We discuss the phenotype in relation to the known tissue-specific expression of Bmp5 and similar morphological abnormalities previously reported in experimental animal models. Our findings suggest a new association between BMP5 variants and a range of developmental anomalies, involving ears, heart and skeleton, thereby increasing understanding of BMP5's role in human development.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeanne Jury, Jean-François Benoist, Madeleine Joubert, Chloé Quelin, Thomas Besnard, Solène Conrad, Claudine Le Vaillant, Stéphane Bézieau, Bertrand Isidor, Tania Attié-Bitach, Benjamin Cogné, Marie Vincent
{"title":"Multiple congenital anomalies in two fetuses with glutathione-synthetase deficit (GSS).","authors":"Jeanne Jury, Jean-François Benoist, Madeleine Joubert, Chloé Quelin, Thomas Besnard, Solène Conrad, Claudine Le Vaillant, Stéphane Bézieau, Bertrand Isidor, Tania Attié-Bitach, Benjamin Cogné, Marie Vincent","doi":"10.1111/cge.14613","DOIUrl":"https://doi.org/10.1111/cge.14613","url":null,"abstract":"<p><p>Glutathione synthetase deficiency is a rare inborn metabolic disease usually caused by biallelic variants in GSS. Clinical severity varies from isolated hemolytic anemia, sometimes associated with chronic metabolic acidosis and 5-oxoprolinuria, to severe neurological phenotypes with neonatal lethality. Here we report on two fetal siblings from two pregnancies with glutathione synthetase deficiency exhibiting similar multiple congenital anomalies associating phocomelia, cleft palate, intra-uterine growth retardation, genito-urinary malformations, and congenital heart defect. Genome sequencing showed that both fetuses were compound heterozygous for two GSS variants: the previously reported pathogenic missense substitution NM_000178.4 c.800G>A p.(Arg267Gln), and a 2.4 kb intragenic deletion NC_000020.11:g.34944530_34946833del. RNA-seq on brain tissue revealed the out-of-frame deletion of the exon 3 and an almost monoallelic expression of the missense variant (88%), suggesting degradation of the deletion-harboring allele by nonsense-mediated mRNA decay. 5-oxoproline (pyroglutamic acid) levels in amniotic fluid were elevated, suggesting an alteration of the gamma-glutamyl cycle, and corroborating the pathogenicity of the two GSS variants. Only one case of glutathione synthetase deficiency with limb malformations has previously been reported, in a newborn homozygous for the c.800G>A variant. Thus, our data allow us to discuss a potential phenotypic extension of glutathione synthetase deficiency, with a possible involvement of the c.800G>A variant.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karina C Silveira, Anastasia Ambrose, Taryn Athey, Sherryl Taylor, Saadet Mercimek-Andrews, Peter Kannu
{"title":"Dissecting CASK: Novel splice site variant associated with male MICPCH phenotype.","authors":"Karina C Silveira, Anastasia Ambrose, Taryn Athey, Sherryl Taylor, Saadet Mercimek-Andrews, Peter Kannu","doi":"10.1111/cge.14610","DOIUrl":"https://doi.org/10.1111/cge.14610","url":null,"abstract":"<p><p>CASK (MIM#300172), encoding a calcium/calmodulin-dependent serine protein kinase, is crucial for synaptic transmission and gene regulation during neural development. Pathogenic variants of CASK are known to cause several neurodevelopmental disorders, including X-linked intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH). This study introduces a novel, de novo synonymous CASK variant (NM_001367721.1: c.1737G>A, p.(Glu579=)), discovered in a male patient diagnosed with MICPCH, characterized by microcephaly, developmental delay, visual impairment, and myoclonic seizures. The variant disrupts a donor splice-site at the end of exon 18. Transcriptomic analysis of blood identified 12 different CASK transcripts secondary to the synonymous variant. Nearly one third of these transcripts were predicted to result in nonsense mediated decay or protein degradation. Protein modeling revealed structural alterations in the PDZ functional domain of CASK, due to exon 18 deletion. Our findings highlight the utility of transcriptomic analysis in demonstrating the underlying disease mechanism in neurodevelopmental disorders.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Childhood glaucoma: Implications for genetic counselling.","authors":"Giorgina Maxwell, Emmanuelle Souzeau","doi":"10.1111/cge.14603","DOIUrl":"https://doi.org/10.1111/cge.14603","url":null,"abstract":"<p><p>Childhood glaucoma is a heterogeneous group of ocular disorders defined by an age of onset from birth to 18 years. These vision-threatening disorders require early diagnosis, timely treatment, and lifelong management to maintain vision and minimise irreversible blindness. The genetics of childhood glaucoma is complex with both phenotypic and genetic heterogeneity. The purpose of this review is to summarise the different types of childhood glaucoma and their genetic architecture to aid in the genetic counselling process with patients and their families. We provide an overview of associated syndromes and discuss implications for genetic counselling, including genetic testing strategies, cascade genetic testing, and reproductive options.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Miriam Bauwens, Vincent De Man, Isabelle Audo, Irina Balikova, Wadih M Zein, Vasily Smirnov, Sebastian Held, Sascha Vermeer, Elke Loos, Julie Jacob, Ingele Casteels, Julie Désir, Fanny Depasse, Stijn Van de Sompele, Mattias Van Heetvelde, Marieke De Bruyne, Camille Andrieu, Christel Condroyer, Aline Antonio, Robert Hufnagel, Ana Luísa Carvalho, João Pedro Marques, Christina Zeitz, Elfride De Baere, Markus Damme
{"title":"Expanding the genetic landscape of Usher syndrome type IV caused by pathogenic ARSG variants.","authors":"Miriam Bauwens, Vincent De Man, Isabelle Audo, Irina Balikova, Wadih M Zein, Vasily Smirnov, Sebastian Held, Sascha Vermeer, Elke Loos, Julie Jacob, Ingele Casteels, Julie Désir, Fanny Depasse, Stijn Van de Sompele, Mattias Van Heetvelde, Marieke De Bruyne, Camille Andrieu, Christel Condroyer, Aline Antonio, Robert Hufnagel, Ana Luísa Carvalho, João Pedro Marques, Christina Zeitz, Elfride De Baere, Markus Damme","doi":"10.1111/cge.14614","DOIUrl":"https://doi.org/10.1111/cge.14614","url":null,"abstract":"<p><p>Usher syndrome (USH) is the most common cause of deafblindness. USH is autosomal recessively inherited and characterized by rod-cone dystrophy or retinitis pigmentosa (RP), often accompanied by sensorineural hearing loss. Variants in >15 genes have been identified as causative for clinically and genetically distinct subtypes. Among the ultra-rare and recently discovered genes is ARSG, coding for the lysosomal sulfatase Arylsulfatase G. This subtype was assigned as \"USH IV\" with a late onset of RP and usually late-onset progressive SNHL without vestibular involvement. Here, we describe nine new subjects and the clinical description of four cases with the USH IV phenotype bearing seven novel and two known pathogenic variants. Functional experiments indicated the complete loss of sulfatase enzymatic activity upon ectopic expression of mutated ARSG cDNA. Interestingly, we identified a homozygous missense variant, p.(Arg99His), previously described in dogs with neuronal ceroid lipofuscinosis. Our study expands the genetic landscape of ARSG-USH IV and the number of known subjects by more than 30%. These findings highlight that USH IV likely has been underdiagnosed and emphasize the need to test molecularly unresolved subjects with deafblindness syndrome. Finally, testing of ARSG should be considered for the genetic work-up of apparent isolated inherited retinal diseases.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jair Tenorio-Castano, Elena Mansilla Aparicio, Fe Amalia García Santiago, Cherise M Klotz, Rita María Regojo, Estefanía Anguita, Erin Ryan, Jane Juusola, Beatriz Herrero, Pedro Arias, Alejandro Parra, Patricia Pascual, Natalia Gallego, Mario Cazalla, Roberto Rodriguez-González, Eugenia Antolín, Julián Nevado, Víctor L Ruiz-Perez, Pablo Lapunzina
{"title":"Non-immune hydrops fetalis is associated with bi-allelic pathogenic variants in the MYB Binding Protein 1a (MYBBP1A) gene.","authors":"Jair Tenorio-Castano, Elena Mansilla Aparicio, Fe Amalia García Santiago, Cherise M Klotz, Rita María Regojo, Estefanía Anguita, Erin Ryan, Jane Juusola, Beatriz Herrero, Pedro Arias, Alejandro Parra, Patricia Pascual, Natalia Gallego, Mario Cazalla, Roberto Rodriguez-González, Eugenia Antolín, Julián Nevado, Víctor L Ruiz-Perez, Pablo Lapunzina","doi":"10.1111/cge.14601","DOIUrl":"https://doi.org/10.1111/cge.14601","url":null,"abstract":"<p><p>Non-immune hydrops fetalis (NIHF) is a rare entity characterized by excessive accumulation of fluid within the fetal extravascular compartments and body cavities. Here we present two intrauterine fetal demises with NIHF presenting with oligohydramnios, cystic hygroma, pleural effusion, and generalized hydrops with predominance of subcutaneous edema. The fetuses also presented with ascites, severe and precocious IUGR and skeletal anomalies. Whole exome sequencing was applied in order to screen for a possible genetic cause. The results identified biallelic variants in MYBBP1A in both fetuses. A previous report described another case with a similar phenotype having compound heterozygous variants in the same gene. The protein encoded by MYBBP1A is involved in several cellular processes including the synthesis of ribosomal DNA, the response to nucleolar stress, and tumor suppression. Our functional protein analysis through immunohistochemistry indicates that MYBBP1A is a gene expressed during fetal stages. Altogether, we concluded that MYBBP1A is associated with the development of hydrops fetalis. More cases and further studies are necessary to understand the role of this gene and the mechanism associated with NIHF.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marlène Malbos, Gabriella Vera, Harsh Sheth, Rhonda E Schnur, Aurélien Juven, Anne-Claire Brehin, Jayesh Sheth, Ajit Gandhi, Faye L Shapiro, Ange-Line Bruel, Florent Marguet, Amber Begtrup, Kristin G Monaghan, Hana Safraou, Marie Brasseur-Daudruy, Frédéric Tran Mau-Them, Yannis Duffourd, Laurence Faivre, Christel Thauvin-Robinet, Paul J Benke, Christophe Philippe
{"title":"SCYL2-related autosomal recessive neurodevelopmental disorders: Arthrogryposis multiplex congenita-4 and beyond?","authors":"Marlène Malbos, Gabriella Vera, Harsh Sheth, Rhonda E Schnur, Aurélien Juven, Anne-Claire Brehin, Jayesh Sheth, Ajit Gandhi, Faye L Shapiro, Ange-Line Bruel, Florent Marguet, Amber Begtrup, Kristin G Monaghan, Hana Safraou, Marie Brasseur-Daudruy, Frédéric Tran Mau-Them, Yannis Duffourd, Laurence Faivre, Christel Thauvin-Robinet, Paul J Benke, Christophe Philippe","doi":"10.1111/cge.14608","DOIUrl":"https://doi.org/10.1111/cge.14608","url":null,"abstract":"<p><p>SCY1-like protein 2 (SCYL2) is a member of the SCY1-like pseudokinase family which regulates secretory protein trafficking. It plays a crucial role in the nervous system by suppressing excitotoxicity in the developing brain. Scyl2 knockout mice have excess prenatal mortality and survivors show severe neurological dysfunction. Bi-allelic loss-of-function (LOF) variants in SCYL2 were recently associated with arthrogryposis multiplex congenita-4 (AMC4) following the report of 6 individuals from two consanguineous unrelated families. The AMC4 phenotype described included severe arthrogryposis, corpus callosum agenesis, epilepsy and frequently, early death. We describe here two additional similarly affected individuals with AMC4, including one diagnosed in the prenatal period, with bi-allelic LOF variants in SCYL2, and two individuals homozygous for missense variants in the protein kinase domain of SCYL2 and presenting with developmental delay only. Our study confirms the association of SCYL2 with AMC4 and suggests a milder phenotype can occur, extending the phenotypic spectrum of autosomal recessive SCYL2-related disorders.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Novel PLEC variants associated with infantile cholestasis.","authors":"Phawin Kor-Anantakul, Huey-Ling Chen, Ya-Hui Chen, Chupong Ittiwut, Rungnapa Ittiwut, Nataruks Chaijitraruch, Kanya Suphapeetiporn, Voranush Chongsrisawat","doi":"10.1111/cge.14611","DOIUrl":"https://doi.org/10.1111/cge.14611","url":null,"abstract":"<p><p>Plectin is a cytoskeletal linker of intermediate filaments, encoded by the PLEC gene. Recently, plectin mutations have been identified in a pair of siblings with progressive familial intrahepatic cholestasis. Here, we reported two unrelated infants with plectinopathy causing cholestatic jaundice with novel variants in the PLEC gene. Trio exome sequencing identified compound heterozygous variants in the PLEC gene for each patient: c.71-11768C>T and c.4331G>T (p.Arg1444Leu) in Patient 1, and c.592C>T (p.Arg198Trp) and c.4322G>A (p.Arg1441His) in Patient 2. Immunofluorescence staining of liver samples from both patients revealed scattered signals of plectin in the cytoplasm of hepatocytes and reduced colocalization of plectin and cytokeratin 8. This study not only underscores the involvement of plectin in cholestasis but also highlights the utility of exome sequencing as a powerful diagnostic tool in identifying genetic underpinnings of infantile cholestasis.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Khemika K Sudnawa, Nicolò Pini, Wenxing Li, Cara H Kanner, Joseph Ryu, Sean Calamia, Jennifer M Bain, Sylvie Goldman, Jacqueline Montes, Yufeng Shen, Wendy K Chung
{"title":"Clinical characteristics, longitudinal adaptive functioning, and association with electroencephalogram activity in PPP2R5D-related neurodevelopmental disorder.","authors":"Khemika K Sudnawa, Nicolò Pini, Wenxing Li, Cara H Kanner, Joseph Ryu, Sean Calamia, Jennifer M Bain, Sylvie Goldman, Jacqueline Montes, Yufeng Shen, Wendy K Chung","doi":"10.1111/cge.14612","DOIUrl":"https://doi.org/10.1111/cge.14612","url":null,"abstract":"<p><p>Protein phosphatase 2 regulatory subunit B56δ related neurodevelopmental disorder (PPP2R5D-related NDD) is largely caused by de novo heterozygous missense PPP2R5D variants. We report medical characteristics, longitudinal adaptive functioning, and in-person neurological, motor, cognitive, and electroencephalogram (EEG) activity for PPP2R5D-related NDD. Forty-two individuals (median age 6 years, range = 0.8-25.3) with pathogenic/likely pathogenic PPP2R5D variants were assessed, and almost all variants were missense (97.6%) and de novo (85.7%). Common clinical symptoms were developmental delay, hypotonia, macrocephaly, seizures, autism, behavioral challenges, and sleep problems. The mean Gross motor functional measure-66 was 60.2 ± 17.3% and the mean Revised upper limb module score was 25.9 ± 8.8. The Vineland-3 adaptive behavior composite score (VABS-3 ABC) at baseline was low (M = 61.7 ± 16.8). VABS-3 growth scale value scores increased from baseline in all subdomains (range = 0.6-5.9) after a mean follow-up of 1.3 ± 0.3 years. EEG beta and gamma power were negatively correlated with VABS-3 score; p < 0.05. Individuals had a mean Quality-of-life inventory-disability score of 74.7 ± 11.4. Twenty caregivers (80%) had a risk of burnout based on the Caregiver burden inventory. Overall, the most common clinical manifestations of PPP2R5D-related NDD were impaired cognitive, adaptive function, and motor skills; and EEG activity was associated with adaptive functioning. This clinical characterization describes the natural history in preparation for clinical trials.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eliane Chouery, Cybel Mehawej, Aline Mansour, Sandra Corbani, Rima Korban, Richard Zalloum, Andre Megarbane
{"title":"Expanding the phenotypes of ABL1 deficiency syndromes: When mutations in different isoforms Lead to different diseases.","authors":"Eliane Chouery, Cybel Mehawej, Aline Mansour, Sandra Corbani, Rima Korban, Richard Zalloum, Andre Megarbane","doi":"10.1111/cge.14609","DOIUrl":"https://doi.org/10.1111/cge.14609","url":null,"abstract":"<p><p>All reported ABL1 gain of function and loss of function (LOF) variants, impact both isoforms 1a and 1b. Our findings suggest that LOF variants affecting solely ABL1 isoform 1b may lead to a distinct autosomal recessive new phenotype.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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