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Reijnders, M.R.* ; 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.D.* ; Smeets, E.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.R.* ; Lönnqvist, T.* ; Isohanni, P.* ; Williams, S.* ; Ruhoy, I.* ; Carvalho, K.S.* ; Dowling, J.J.* ; Lev, D.L.* ; Sterbova, K.* ; Lassuthova, P.* ; Neupauerová, J.* ; Waugh, J.L.* ; Keros, S.* ; Clayton-Smith, J.* ; Smithson, S.F.* ; Brunner, H.G.* ; van Hoeckel, C.* ; Anderson, M.D.* ; Clowes, V.E.* ; Siu, V.M.* ; Ddd Study, T.* ; Selber, P.* ; Leventer, R.J.* ; Nellaker, C.* ; Niessing, D. ; Hunt, D.T.E.* ; Baralle, D.*

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

J. Med. Genet. 55, 104-113 (2017)
Verlagsversion DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Pura Syndrome ; Epilepsy And Seizures ; Hypotonia ; Intellectual Disability ; Neonatal Problems; 5q31.3 Microdeletion Syndrome; Postnatal Brain-development; Alpha; Reveals; Patient; Genes
ISSN (print) / ISBN 0022-2593
e-ISSN 1468-6244
Quellenangaben Band: 55, Heft: 2, Seiten: 104-113 Artikelnummer: , Supplement: ,
Verlag BMJ Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed