Paediatrics Publications
PURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literature
Document Type
Article
Publication Date
2-1-2018
Journal
Journal of Medical Genetics
Volume
55
Issue
2
First Page
104
Last Page
113
URL with Digital Object Identifier
https://doi.org/10.1136/jmedgenet-2017-104946
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
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
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.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Notes
Article available at Journal of Medical Genetics, Vol. 55(2).
https://doi.org/10.1136/jmedgenet-2017-104946
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.