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dc.contributor.authorReijnders, MRF
dc.contributor.authorJanowski, R
dc.contributor.authorAlvi, M
dc.contributor.authorSelf, JE
dc.contributor.authorvan Essen, TJ
dc.contributor.authorVreeburg, M
dc.contributor.authorRouhl, RPW
dc.contributor.authorStevens, SJC
dc.contributor.authorStegmann, APA
dc.contributor.authorSchieving, J
dc.contributor.authorPfundt, R
dc.contributor.authorvan Dijk, K
dc.contributor.authorSmeets, E
dc.contributor.authorStumpel, CTRM
dc.contributor.authorBok, LA
dc.contributor.authorCobben, JM
dc.contributor.authorEngelen, M
dc.contributor.authorMansour, S
dc.contributor.authorWhiteford, M
dc.contributor.authorChandler, KE
dc.contributor.authorDouzgou, S
dc.contributor.authorCooper, NS
dc.contributor.authorTan, E-C
dc.contributor.authorFoo, R
dc.contributor.authorLai, AHM
dc.contributor.authorRankin, J
dc.contributor.authorGreen, A
dc.contributor.authorLoennqvist, T
dc.contributor.authorIsohanni, P
dc.contributor.authorWilliams, S
dc.contributor.authorRuhoy, I
dc.contributor.authorCarvalho, KS
dc.contributor.authorDowling, JJ
dc.contributor.authorLev, DL
dc.contributor.authorSterbova, K
dc.contributor.authorLassuthova, P
dc.contributor.authorNeupauerova, J
dc.contributor.authorWaugh, JL
dc.contributor.authorKeros, S
dc.contributor.authorClayton-Smith, J
dc.contributor.authorSmithson, SF
dc.contributor.authorBrunner, HG
dc.contributor.authorvan Hoeckel, C
dc.contributor.authorAnderson, M
dc.contributor.authorClowes, VE
dc.contributor.authorSiu, VM
dc.contributor.authorSelber, P
dc.contributor.authorLeventer, RJ
dc.contributor.authorNellaker, C
dc.contributor.authorNiessing, D
dc.contributor.authorHunt, D
dc.contributor.authorBaralle, D
dc.date.accessioned2020-12-21T04:08:15Z
dc.date.available2020-12-21T04:08:15Z
dc.date.issued2018-02-01
dc.identifierpii: jmedgenet-2017-104946
dc.identifier.citationReijnders, 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. ,... Baralle, D. (2018). PURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literature. JOURNAL OF MEDICAL GENETICS, 55 (2), pp.104-113. https://doi.org/10.1136/jmedgenet-2017-104946.
dc.identifier.issn0022-2593
dc.identifier.urihttp://hdl.handle.net/11343/257497
dc.description.abstractBACKGROUND: 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: To 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 genotype-phenotype 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.
dc.languageEnglish
dc.publisherBMJ PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0
dc.titlePURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literature
dc.typeJournal Article
dc.identifier.doi10.1136/jmedgenet-2017-104946
melbourne.affiliation.departmentPaediatrics (RCH)
melbourne.source.titleJournal of Medical Genetics
melbourne.source.volume55
melbourne.source.issue2
melbourne.source.pages104-113
dc.rights.licenseCC BY-NC
melbourne.elementsid1271153
melbourne.contributor.authorLeventer, Richard
dc.identifier.eissn1468-6244
melbourne.accessrightsOpen Access


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