Journal article
PURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literature
Journal of Medical Genetics
01 Jan 2018
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- PURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literature
- Creators
- Margot R. F ReijndersRobert JanowskiMohsan AlviJay E SelfTon J. van EssenMaaike VreeburgRob P. W RouhlServi J. C StevensAlexander P. A StegmannJolanda SchievingRolph PfundtKatinke van DijkEric SmeetsConnie T. R. M StumpelLevinus A BokJan Maarten CobbenMarc EngelenSahar MansourMargo WhitefordKate E ChandlerSofia DouzgouNicola S CooperEne-Choo TanRoger FooAngeline H. M LaiJulia RankinAndrew GreenTuula LoennqvistPirjo IsohanniShelley WilliamsIlene RuhoyKaren S CarvalhoJames J DowlingDorit L LevKatalin SterbovaPetra LassuthovaJana NeupauerovaJeff L WaughSotirios KerosJill Clayton-SmithSarah F SmithsonHan G BrunnerCeciel van HoeckelMel AndersonVirginia E ClowesVictoria Mok SiuPaulo SelberRichard J LeventerChristoffer NellakerDierk NiessingDavid HuntDiana Baralle
- Publication Details
- Journal of Medical Genetics
- Publisher
- Ludwig-Maximilians-Universität München
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000423230800006
- Scopus ID
- 2-s2.0-85042440885
- Other Identifier
- 991021448024104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Genetics & Heredity