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Neuropediatrics 2021; 52(05): 390-393
DOI: 10.1055/s-0040-1715625
Short Communication

Three Individuals with PURA Syndrome in a Cohort of Patients with Neuromuscular Disease

Magdalena Mroczek
1   John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals National Health Service Foundation Trust, Newcastle upon Tyne, United Kingdom
,
Dimitrios Zafeiriou
2   Department of Paediatrics, Aristotle University of Thessaloniki, “Hippokratio” General Hospital, Thessaloniki, Greece
,
Juliana Gurgel-Gianetti
3   Department of Pediatrics, Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
,
Beatriz Vilela Morais de Azevedo
3   Department of Pediatrics, Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
,
Andreas Roos
4   Department of Pediatric Neurology, University of Duisburg-Essen, University Hospital Essen, Faculty of Medicine, Essen, Germany
,
Enrika Bartels
5   Institute of Clinical Genetics and Tumor Genetics, Bonn, Germany
,
Nicolai Kohlschmidt
5   Institute of Clinical Genetics and Tumor Genetics, Bonn, Germany
,
Rahul Phadke
6   Dubowitz Neuromuscular Centre, MRC Centre for Neuromuscular Diseases, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
,
Lucy Feng
6   Dubowitz Neuromuscular Centre, MRC Centre for Neuromuscular Diseases, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
,
Jennifer Duff
1   John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals National Health Service Foundation Trust, Newcastle upon Tyne, United Kingdom
,
Ana Töpf
1   John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals National Health Service Foundation Trust, Newcastle upon Tyne, United Kingdom
,
Volker Straub
1   John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals National Health Service Foundation Trust, Newcastle upon Tyne, United Kingdom
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Abstract

Pur-α protein (PURA) syndrome manifests in early childhood with core features such as neurodevelopmental and speech delay, feeding difficulties, epilepsy, and hypotonia at birth. We identified three cases with PURA syndrome in a cohort of patients with unexplained muscular weakness, presenting with a predominantly neuromuscular and ataxic phenotype. We further characterize the clinical presentation of PURA syndrome including myopathic facies and muscular weakness as the main clinical symptoms in combination with elevated serum creatine kinase levels. Furthermore, we report two novel variants located in the conservative domains PUR-I and PUR-II. For the first time, we present the muscle biopsies of PURA syndrome patients, showing myopathic changes, fiber size variability, and fast fiber atrophy as the key features. PURA syndrome should be taken into consideration as a differential diagnosis in pediatric patients with unexplained muscle weakness.

Keywords

PURA syndrome - fast fiber atrophy - neurodevelopmental delay


Publication History

Received: 07 February 2020

Accepted: 11 June 2020

Article published online:
22 December 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Daniel DC, Johnson EM. PURA, the gene encoding Pur-alpha, member of an ancient nucleic acid-binding protein family with mammalian neurological functions. Gene 2018; 643: 133-143
    CrossrefPubMedGoogle Scholar
  • 2 Johnson EM, Kinoshita Y, Weinreb DB. et al. Role of Pur alpha in targeting mRNA to sites of translation in hippocampal neuronal dendrites. J Neurosci Res 2006; 83 (06) 929-943
    CrossrefPubMedGoogle Scholar
  • 3 Hunt D, Leventer RJ, Simons C. et al; DDD study. Whole exome sequencing in family trios reveals de novo mutations in PURA as a cause of severe neurodevelopmental delay and learning disability. J Med Genet 2014; 51 (12) 806-813
    CrossrefPubMedGoogle Scholar
  • 4 Lee BH, Reijnders MRF, Abubakare O. et al. Expanding the neurodevelopmental phenotype of PURA syndrome. Am J Med Genet A 2018; 176 (01) 56-67
    CrossrefPubMedGoogle Scholar
  • 5 Reijnders MRF, Janowski R, Alvi M. et al. PURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literature. J Med Genet 2018; 55 (02) 104-113
    CrossrefPubMedGoogle Scholar
  • 6 Hunt D, Leventer RJ, Simons C. et al; DDD study. Whole exome sequencing in family trios reveals de novo mutations in PURA as a cause of severe neurodevelopmental delay and learning disability. J Med Genet 2014; 51 (12) 806-813
    CrossrefPubMedGoogle Scholar
  • 7 Johnson EM, Daniel DC, Gordon J. The pur protein family: genetic and structural features in development and disease. J Cell Physiol 2013; 228 (05) 930-937
    CrossrefPubMedGoogle Scholar
  • 8 Lisi EC, Cohn RD. Genetic evaluation of the pediatric patient with hypotonia: perspective from a hypotonia specialty clinic and review of the literature. Dev Med Child Neurol 2011; 53 (07) 586-599
    CrossrefPubMedGoogle Scholar
  • 9 Lalani SR, Zhang J, Schaaf CP. et al. Mutations in PURA cause profound neonatal hypotonia, seizures, and encephalopathy in 5q31.3 microdeletion syndrome. Am J Hum Genet 2014; 95 (05) 579-583
    CrossrefPubMedGoogle Scholar
  • 10 https://www.purasyndrome.org/family . Accessed onNovember 30, 2019
    PubMed