PURA syndrome : clinical delineation and genotype-phenotype study in 32 individuals with review of published literature

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dc.contributor.author Reijnders, Margot R. F.
dc.contributor.author Janowski, Robert
dc.contributor.author Alvi, Mohsan
dc.contributor.author Self, Jay E.
dc.contributor.author van Essen, Ton J.
dc.contributor.author Vreeburg, Maaike
dc.contributor.author Rouhl, Rob P. W.
dc.contributor.author Stevens, Servi J. C.
dc.contributor.author Stegmann, Alexander P. A.
dc.contributor.author Schieving, Jolanda
dc.contributor.author Pfundt, Rolph
dc.contributor.author van Dijk, Katinke
dc.contributor.author Smeets, Eric
dc.contributor.author Stumpel, Connie T. R. M.
dc.contributor.author Bok, Levinus A.
dc.contributor.author Cobben, Jan Maarten
dc.contributor.author Engelen, Marc
dc.contributor.author Mansour, Sahar
dc.contributor.author Whiteford, Margo
dc.contributor.author Chandler, Kate E.
dc.contributor.author Douzgou, Sofia
dc.contributor.author Cooper, Nicola S.
dc.contributor.author Tan, Ene-Choo
dc.contributor.author Foo, Roger
dc.contributor.author Lai, Angeline H. M.
dc.contributor.author Rankin, Julia
dc.contributor.author Green, Andrew
dc.contributor.author Lönnqvist, Tuula
dc.contributor.author Isohanni, Pirjo
dc.contributor.author Williams, Shelley
dc.contributor.author Ruhoy, Ilene
dc.contributor.author Carvalho, Karen S.
dc.contributor.author Dowling, James J.
dc.contributor.author Lev, Dorit L.
dc.contributor.author Sterbova, Katalin
dc.contributor.author Lassuthova, Petra
dc.contributor.author Neupauerova, Jana
dc.contributor.author Waugh, Jeff L.
dc.contributor.author Keros, Sotirios
dc.contributor.author Clayton-Smith, Jill
dc.contributor.author Smithson, Sarah F.
dc.contributor.author Brunner, Han G.
dc.contributor.author van Hoeckel, Ceciel
dc.contributor.author Anderson, Mel
dc.contributor.author Clowes, Virginia E.
dc.contributor.author Siu, Victoria Mok
dc.contributor.author Selber, Paulo
dc.contributor.author Leventer, Richard J.
dc.contributor.author Nellaker, Christoffer
dc.contributor.author Niessing, Dierk
dc.contributor.author DDD Study
dc.date.accessioned 2018-03-13T12:18:01Z
dc.date.available 2018-03-13T12:18:01Z
dc.date.issued 2018-02
dc.identifier.citation Reijnders , M R F , Janowski , R , Alvi , M , Self , J E , van Essen , T J , Vreeburg , M , Rouhl , R P W , Stevens , S J C , Stegmann , A P A , Schieving , J , Pfundt , R , van Dijk , K , Smeets , E , Stumpel , C T R M , Bok , L A , Cobben , J M , Engelen , M , Mansour , S , Whiteford , M , Chandler , K E , Douzgou , S , Cooper , N S , Tan , E-C , Foo , R , Lai , A H M , Rankin , J , Green , A , Lönnqvist , T , Isohanni , P , Williams , S , Ruhoy , I , Carvalho , K S , Dowling , J J , Lev , D L , Sterbova , K , Lassuthova , P , Neupauerova , J , Waugh , J L , Keros , S , Clayton-Smith , J , Smithson , S F , Brunner , H G , van Hoeckel , C , Anderson , M , Clowes , V E , Siu , V M , Selber , P , Leventer , R J , Nellaker , C , Niessing , D & DDD Study 2018 , ' PURA syndrome : clinical delineation and genotype-phenotype study in 32 individuals with review of published literature ' , Journal of Medical Genetics , vol. 55 , no. 2 , pp. 104-113 . https://doi.org/10.1136/jmedgenet-2017-104946
dc.identifier.other PURE: 100281220
dc.identifier.other PURE UUID: 96213ab5-0057-46ee-8298-fbba472606bf
dc.identifier.other WOS: 000423230800006
dc.identifier.other Scopus: 85042440885
dc.identifier.uri http://hdl.handle.net/10138/233379
dc.description.abstract Background De novo mutations in PURA have recently been described to cause PURA syndrome, a neurodevelopmental disorder characterised by severe intellectual disability (ID), epilepsy, feeding difficulties and neonatal hypotonia. Objectives T o delineate the clinical spectrum of PURA syndrome and study genotype-phenotype correlations. Methods Diagnostic or research-based exome or Sanger sequencing was performed in individuals with ID. We systematically collected clinical and mutation data on newly ascertained PURA syndrome individuals, evaluated data of previously reported individuals and performed a computational analysis of photographs. We classified mutations based on predicted effect using 3D in silico models of crystal structures of Drosophila-derived Pur-alpha homologues. Finally, we explored genotypephenotype correlations by analysis of both recurrent mutations as well as mutation classes. Results We report mutations in PURA (purine-rich element binding protein A) in 32 individuals, the largest cohort described so far. Evaluation of clinical data, including 22 previously published cases, revealed that all have moderate to severe ID and neonatal-onset symptoms, including hypotonia (96%), respiratory problems (57%), feeding difficulties (77%), exaggerated startle response (44%), hypersomnolence (66%) and hypothermia (35%). Epilepsy (54%) and gastrointestinal (69%), ophthalmological (51%) and endocrine problems (42%) were observed frequently. Computational analysis of facial photographs showed subtle facial dysmorphism. No strong genotype-phenotype correlation was identified by subgrouping mutations into functional classes. Conclusion We delineate the clinical spectrum of PURA syndrome with the identification of 32 additional individuals. The identification of one individual through targeted Sanger sequencing points towards the clinical recognisability of the syndrome. Genotype-phenotype analysis showed no significant correlation between mutation classes and disease severity. en
dc.format.extent 10
dc.language.iso eng
dc.relation.ispartof Journal of Medical Genetics
dc.rights cc_by_nc
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject ALPHA
dc.subject REVEALS
dc.subject PATIENT
dc.subject GENES
dc.subject 3112 Neurosciences
dc.subject 3124 Neurology and psychiatry
dc.title PURA syndrome : clinical delineation and genotype-phenotype study in 32 individuals with review of published literature en
dc.type Review Article
dc.contributor.organization Clinicum
dc.contributor.organization Children's Hospital
dc.contributor.organization Lastenneurologian yksikkö
dc.contributor.organization University of Helsinki
dc.contributor.organization Research Programs Unit
dc.contributor.organization Anu Wartiovaara / Principal Investigator
dc.contributor.organization Research Programme for Molecular Neurology
dc.contributor.organization HUS Children and Adolescents
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1136/jmedgenet-2017-104946
dc.relation.issn 0022-2593
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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