Sporadic Infantile Epileptic Encephalopathy Caused by Mutations in PCDH19 Resembles Dravet Syndrome but Mainly Affects Females
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{"title"=>"Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles dravet syndrome but mainly affects females", "type"=>"journal", "authors"=>[{"first_name"=>"Christel", "last_name"=>"Depienne", "scopus_author_id"=>"16027963900"}, {"first_name"=>"Delphine", "last_name"=>"Bouteiller", "scopus_author_id"=>"14029525100"}, {"first_name"=>"Boris", "last_name"=>"Keren", "scopus_author_id"=>"23009044300"}, {"first_name"=>"Emmanuel", "last_name"=>"Cheuret", "scopus_author_id"=>"22633592400"}, {"first_name"=>"Karine", "last_name"=>"Poirier", "scopus_author_id"=>"6603923387"}, {"first_name"=>"Oriane", "last_name"=>"Trouillard", "scopus_author_id"=>"6508018269"}, {"first_name"=>"Baya", "last_name"=>"Benyahia", "scopus_author_id"=>"7003754118"}, {"first_name"=>"Chloé", "last_name"=>"Quelin", "scopus_author_id"=>"26028026700"}, {"first_name"=>"Wassila", "last_name"=>"Carpentier", "scopus_author_id"=>"23767878700"}, {"first_name"=>"Sophie", "last_name"=>"Julia", "scopus_author_id"=>"6603716549"}, {"first_name"=>"Alexandra", "last_name"=>"Afenjar", "scopus_author_id"=>"22949682700"}, {"first_name"=>"Agnès", "last_name"=>"Gautier", "scopus_author_id"=>"7006382887"}, {"first_name"=>"François", "last_name"=>"Rivier", "scopus_author_id"=>"7004288865"}, {"first_name"=>"Sophie", "last_name"=>"Meyer", "scopus_author_id"=>"7402775049"}, {"first_name"=>"Patrick", "last_name"=>"Berquin", "scopus_author_id"=>"6701537734"}, {"first_name"=>"Marie", "last_name"=>"Hélias", "scopus_author_id"=>"6507449887"}, {"first_name"=>"Isabelle", "last_name"=>"Py", "scopus_author_id"=>"12808246600"}, {"first_name"=>"Serge", "last_name"=>"Rivera", "scopus_author_id"=>"57197228478"}, {"first_name"=>"Nadia", "last_name"=>"Bahi-Buisson", "scopus_author_id"=>"6506667951"}, {"first_name"=>"Isabelle", "last_name"=>"Gourfinkel-An", "scopus_author_id"=>"6603173006"}, {"first_name"=>"Cécile", "last_name"=>"Cazeneuve", "scopus_author_id"=>"7003402642"}, {"first_name"=>"Merle", "last_name"=>"Ruberg", "scopus_author_id"=>"7006270693"}, {"first_name"=>"Alexis", "last_name"=>"Brice", "scopus_author_id"=>"8065204700"}, {"first_name"=>"Rima", "last_name"=>"Nabbout", "scopus_author_id"=>"6701756441"}, {"first_name"=>"Eric", "last_name"=>"Leguern", "scopus_author_id"=>"7006086128"}], "year"=>2009, "source"=>"PLoS Genetics", "identifiers"=>{"pmid"=>"19214208", "doi"=>"10.1371/journal.pgen.1000381", "sgr"=>"61449230751", "isbn"=>"10.1371/journal.pgen.1000381", "scopus"=>"2-s2.0-61449230751", "issn"=>"15537390", "pui"=>"354253481"}, "id"=>"2cdffe67-2844-3b05-9278-ea44bc7f9ae7", "abstract"=>"Dravet syndrome (DS) is a genetically determined epileptic encephalopathy mainly caused by de novo mutations in the SCN1A gene. Since 2003, we have performed molecular analyses in a large series of patients with DS, 27% of whom were negative for mutations or rearrangements in SCN1A. In order to identify new genes responsible for the disorder in the SCN1A-negative patients, 41 probands were screened for micro-rearrangements with Illumina high-density SNP microarrays. A hemizygous deletion on chromosome Xq22.1, encompassing the PCDH19 gene, was found in one male patient. To confirm that PCDH19 is responsible for a Dravet-like syndrome, we sequenced its coding region in 73 additional SCN1A-negative patients. Nine different point mutations (four missense and five truncating mutations) were identified in 11 unrelated female patients. In addition, we demonstrated that the fibroblasts of our male patient were mosaic for the PCDH19 deletion. Patients with PCDH19 and SCN1A mutations had very similar clinical features including the association of early febrile and afebrile seizures, seizures occurring in clusters, developmental and language delays, behavioural disturbances, and cognitive regression. There were, however, slight but constant differences in the evolution of the patients, including fewer polymorphic seizures (in particular rare myoclonic jerks and atypical absences) in those with PCDH19 mutations. These results suggest that PCDH19 plays a major role in epileptic encephalopathies, with a clinical spectrum overlapping that of DS. This disorder mainly affects females. The identification of an affected mosaic male strongly supports the hypothesis that cellular interference is the pathogenic mechanism.", "link"=>"http://www.mendeley.com/research/sporadic-infantile-epileptic-encephalopathy-caused-mutations-pcdh19-resembles-dravet-syndrome-mainly", "reader_count"=>129, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>11, "Researcher"=>32, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>25, "Student > Postgraduate"=>4, "Other"=>13, "Student > Master"=>15, "Student > Bachelor"=>15, "Lecturer"=>3, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>11, "Researcher"=>32, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>25, "Student > Postgraduate"=>4, "Other"=>13, "Student > Master"=>15, "Student > Bachelor"=>15, "Lecturer"=>3, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>7, "Biochemistry, Genetics and Molecular Biology"=>11, "Agricultural and Biological Sciences"=>55, "Medicine and Dentistry"=>40, "Neuroscience"=>9, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Psychology"=>1, "Chemistry"=>1, "Computer Science"=>2, "Earth and Planetary Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>40}, "Neuroscience"=>{"Neuroscience"=>9}, "Chemistry"=>{"Chemistry"=>1}, "Psychology"=>{"Psychology"=>1}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>55}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>11}, "Unspecified"=>{"Unspecified"=>7}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"Colombia"=>1, "Netherlands"=>2, "Sweden"=>1, "United States"=>1, "Brazil"=>1, "France"=>1, "Australia"=>1, "Ethiopia"=>1, "Germany"=>1}, "group_count"=>5}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/908901"], "description"=>"<p>Above: mutations identified in this study; Below: mutations identified by Dibbens et al. (2008). SP: signal peptide; EC: extracellular cadherin domain; TM: transmembrane domain; CM1 and CM2: cytoplasmic domains 1 and 2.</p>", "links"=>[], "tags"=>["mutations"], "article_id"=>579334, "categories"=>["Cell Biology", "Genetics", "Neuroscience"], "users"=>["Christel Depienne", "Delphine Bouteiller", "Boris Keren", "Emmanuel Cheuret", "Karine Poirier", "Oriane Trouillard", "Baya Benyahia", "Chloé Quelin", "Wassila Carpentier", "Sophie Julia", "Alexandra Afenjar", "Agnès Gautier", "François Rivier", "Sophie Meyer", "Patrick Berquin", "Marie Hélias", "Isabelle Py", "Serge Rivera", "Nadia Bahi-Buisson", "Isabelle Gourfinkel-An", "Cécile Cazeneuve", "Merle Ruberg", "Alexis Brice", "Rima Nabbout", "Eric Leguern"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000381.g005", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_representation_of_the_point_mutations_identified_in_the_PCDH19_gene_/579334", "title"=>"Schematic representation of the point mutations identified in the <i>PCDH19</i> gene.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 06:55:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/908402"], "description"=>"<p>A) Identification of a hemizygous Xq22.1 deletion with a 370 K SNP microarray (Illumina): Y-axes represent Log R ratio (above) and B allele frequency (below); the X-axis indicates the position on the X chromosome. The red line (log R ratio profile) corresponds to the median smoothing series (Beadstudio). B) Analysis of the patient and his mother with CGH microarrays (Nimblegen), showing that the deletion occurred de novo. Indicated genomic positions are based upon the Ensembl Genome Browser. Black horizontal bars (below) represent the gene (<i>PCDH19</i>) and pseudogenes comprised in the deleted region.</p>", "links"=>[], "tags"=>["deletion", "encompassing"], "article_id"=>578807, "categories"=>["Cell Biology", "Genetics", "Neuroscience"], "users"=>["Christel Depienne", "Delphine Bouteiller", "Boris Keren", "Emmanuel Cheuret", "Karine Poirier", "Oriane Trouillard", "Baya Benyahia", "Chloé Quelin", "Wassila Carpentier", "Sophie Julia", "Alexandra Afenjar", "Agnès Gautier", "François Rivier", "Sophie Meyer", "Patrick Berquin", "Marie Hélias", "Isabelle Py", "Serge Rivera", "Nadia Bahi-Buisson", "Isabelle Gourfinkel-An", "Cécile Cazeneuve", "Merle Ruberg", "Alexis Brice", "Rima Nabbout", "Eric Leguern"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000381.g001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_of_a_deletion_encompassing_PCDH19_in_a_male_patient_/578807", "title"=>"Identification of a deletion encompassing <i>PCDH19</i> in a male patient.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 06:52:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/908697"], "description"=>"<p>del/+, m/+ or v/+ denote individuals heterozygous for the deletion, mutation or variant, respectively; +/+ denotes individuals carrying homozygous wild-type alleles. Squares represent males, circles females; filled black symbols: patients diagnosed as having Dravet syndrome; right black half: Cognitive delay or impairment; left grey half: adolescence-onset idiopathic epilepsy. Dots in the middle of the squares indicate unaffected mutation carriers. The arrows indicate the index cases.</p>", "links"=>[], "tags"=>["segregation", "deletion"], "article_id"=>579128, "categories"=>["Cell Biology", "Genetics", "Neuroscience"], "users"=>["Christel Depienne", "Delphine Bouteiller", "Boris Keren", "Emmanuel Cheuret", "Karine Poirier", "Oriane Trouillard", "Baya Benyahia", "Chloé Quelin", "Wassila Carpentier", "Sophie Julia", "Alexandra Afenjar", "Agnès Gautier", "François Rivier", "Sophie Meyer", "Patrick Berquin", "Marie Hélias", "Isabelle Py", "Serge Rivera", "Nadia Bahi-Buisson", "Isabelle Gourfinkel-An", "Cécile Cazeneuve", "Merle Ruberg", "Alexis Brice", "Rima Nabbout", "Eric Leguern"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000381.g003", "stats"=>{"downloads"=>7, "page_views"=>177, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pedigrees_of_the_families_and_segregation_analysis_of_the_PCDH19_deletion_and_point_mutations_/579128", "title"=>"Pedigrees of the families and segregation analysis of the <i>PCDH19</i> deletion and point mutations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 06:54:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/908519"], "description"=>"<p>A) Sequence electropherograms of the mutations and the missense variant (c.3319C>G/p.Arg1107Gly) identified in association with the c.859G>T/p.Glu287X nonsense mutation. The mutation nomenclature is based on the <i>PCDH19</i> transcript reference EF676096. Nucleotides are numbered according to the cDNA with +1 corresponding to the A of the ATG translation initiation codon in the reference sequence, according to the journal guidelines (<a href=\"http://www.hgvs.org/mutnomen\" target=\"_blank\">www.hgvs.org/mutnomen</a>). B) Alignment of the regions surrounding the mutations (indicated by an arrow) in orthologous and paralogous proteins, showing the high conservation of each affected amino-acid in vertebrates and in the delta protocadherin paralogous genes.</p>", "links"=>[], "tags"=>["mutations", "11", "patients"], "article_id"=>578953, "categories"=>["Cell Biology", "Genetics", "Neuroscience"], "users"=>["Christel Depienne", "Delphine Bouteiller", "Boris Keren", "Emmanuel Cheuret", "Karine Poirier", "Oriane Trouillard", "Baya Benyahia", "Chloé Quelin", "Wassila Carpentier", "Sophie Julia", "Alexandra Afenjar", "Agnès Gautier", "François Rivier", "Sophie Meyer", "Patrick Berquin", "Marie Hélias", "Isabelle Py", "Serge Rivera", "Nadia Bahi-Buisson", "Isabelle Gourfinkel-An", "Cécile Cazeneuve", "Merle Ruberg", "Alexis Brice", "Rima Nabbout", "Eric Leguern"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000381.g002", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Detection_of_9_different_point_mutations_of_PCDH19_in_11_female_patients_by_direct_sequencing_/578953", "title"=>"Detection of 9 different point mutations of <i>PCDH19</i> in 11 female patients by direct sequencing.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 06:53:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/908797"], "description"=>"<p>(A) Absence of the specific Xq22.1 probe site on metaphase chromosomes in peripheral blood lymphocytes (PBL); (B) In fibroblasts, presence of one hybridization spot in 53% of the cells and absence of signal in the remaining 47%; C) and D) FISH analysis on PBL (C) and fibroblasts (D) of a female control. <i>PCDH19</i>-specific signals (red) are indicated by arrowheads. Magnification ×1000.</p>", "links"=>[], "tags"=>["deletion", "somatic", "mosaicism"], "article_id"=>579226, "categories"=>["Cell Biology", "Genetics", "Neuroscience"], "users"=>["Christel Depienne", "Delphine Bouteiller", "Boris Keren", "Emmanuel Cheuret", "Karine Poirier", "Oriane Trouillard", "Baya Benyahia", "Chloé Quelin", "Wassila Carpentier", "Sophie Julia", "Alexandra Afenjar", "Agnès Gautier", "François Rivier", "Sophie Meyer", "Patrick Berquin", "Marie Hélias", "Isabelle Py", "Serge Rivera", "Nadia Bahi-Buisson", "Isabelle Gourfinkel-An", "Cécile Cazeneuve", "Merle Ruberg", "Alexis Brice", "Rima Nabbout", "Eric Leguern"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000381.g004", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_FISH_analysis_of_the_PCDH19_deletion_in_the_male_patient_showing_somatic_mosaicism_in_fibroblasts_/579226", "title"=>"FISH analysis of the <i>PCDH19</i> deletion in the male patient showing somatic mosaicism in fibroblasts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 06:54:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/909008"], "description"=>"<p>A) In normal individuals, characterized by a homogeneous population of <i>PCDH19</i>-positive cells, neurons are able to form normal neuronal networks; B) In mutated male patients, hemizygosity leads to a homogeneous population of <i>PCDH19</i>-negative cells; in this condition, neurons preserve the ability to form normal neuronal networks; C) In heterozygous mutated females, random X inactivation leads to the co-existence of two <i>PCDH19</i>-positive and <i>PCDH19</i>-negative cell populations. These two cell populations cause divergent cell sorting and migration (due to attractive or repulsive interactions) and lead to abnormal neuronal networks. Somatic mosaicism in mutated males gives rise to the same pathological situation. The precise mechanisms by which the neuronal networks are altered are still unknown.</p>", "links"=>[], "tags"=>["cellular", "interference"], "article_id"=>579435, "categories"=>["Cell Biology", "Genetics", "Neuroscience"], "users"=>["Christel Depienne", "Delphine Bouteiller", "Boris Keren", "Emmanuel Cheuret", "Karine Poirier", "Oriane Trouillard", "Baya Benyahia", "Chloé Quelin", "Wassila Carpentier", "Sophie Julia", "Alexandra Afenjar", "Agnès Gautier", "François Rivier", "Sophie Meyer", "Patrick Berquin", "Marie Hélias", "Isabelle Py", "Serge Rivera", "Nadia Bahi-Buisson", "Isabelle Gourfinkel-An", "Cécile Cazeneuve", "Merle Ruberg", "Alexis Brice", "Rima Nabbout", "Eric Leguern"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000381.g006", "stats"=>{"downloads"=>6, "page_views"=>38, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_illustration_of_the_cellular_interference_mechanism_associated_with_PCDH19_mutations_/579435", "title"=>"Schematic illustration of the cellular interference mechanism associated with <i>PCDH19</i> mutations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 06:56:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/909078"], "description"=>"<p>2*: patient N 06 1258 is the sister of patient N 06 1257 (index case); PMD = psychomotor development, Nl = normal, F = febrile, unit = unilateral, GTC = generalized tonic-clonic, W-S = words-sentences, abs = absent, AED = anti epileptic drugs.</p>", "links"=>[], "tags"=>["characteristics", "patients"], "article_id"=>579514, "categories"=>["Cell Biology", "Genetics", "Neuroscience"], "users"=>["Christel Depienne", "Delphine Bouteiller", "Boris Keren", "Emmanuel Cheuret", "Karine Poirier", "Oriane Trouillard", "Baya Benyahia", "Chloé Quelin", "Wassila Carpentier", "Sophie Julia", "Alexandra Afenjar", "Agnès Gautier", "François Rivier", "Sophie Meyer", "Patrick Berquin", "Marie Hélias", "Isabelle Py", "Serge Rivera", "Nadia Bahi-Buisson", "Isabelle Gourfinkel-An", "Cécile Cazeneuve", "Merle Ruberg", "Alexis Brice", "Rima Nabbout", "Eric Leguern"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000381.t001", "stats"=>{"downloads"=>6, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_characteristics_of_patients_with_PCDH19_mutations_/579514", "title"=>"Clinical characteristics of patients with <i>PCDH19</i> mutations.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 06:56:28"}

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  • {"unique-ip"=>"23", "full-text"=>"27", "pdf"=>"8", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"30", "full-text"=>"31", "pdf"=>"9", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"21", "full-text"=>"24", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"26", "full-text"=>"29", "pdf"=>"10", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"18", "full-text"=>"22", "pdf"=>"8", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"24", "full-text"=>"37", "pdf"=>"10", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
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  • {"unique-ip"=>"26", "full-text"=>"23", "pdf"=>"12", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"39", "full-text"=>"39", "pdf"=>"11", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"27", "full-text"=>"26", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}

Relative Metric

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