A novel IRF2BPL truncating variant is associated with endolysosomal storage

  • Monia Ginevrino
  • Roberta Battini
  • Sara Nuovo
  • Alessandro Simonati
  • Alessia Micalizzi
  • Ilaria Contaldo
  • Valentina Serpieri
  • Enza Maria ValenteEmail author
Short Communication


De novo mutations in the IRF2BPL gene have been identified to date in 18 patients presenting with neuromotor regression, epilepsy and variable neurological signs. Here, we report a female child carrying a novel heterozygous truncating variant in IRF2BPL. Following normal development for two and half years, she developed a progressive neurological condition with psychomotor regression, dystonic tetraparesis with hyperkinetic movements, but no overt epilepsy. Skin biopsy revealed enlarged lysosomes containing granular and tubular material, suggestive of a lysosomal storage disorder. This case expands the IRF2BPL phenotypic spectrum, for the first time providing evidence of endolysosomal storage.


IRF2BPL De novo mutations Neurodegenerative disorders Lysosomal storage disorders Neuronal ceroid lipofuscinosis 



This work was funded by the European Research Council (ERC Starting Grant 260888), the Pierfranco and Luisa Mariani Foundation (PADAPORT project) and the Italian Ministry of Health (Ricerca Finalizzata 2013 NET-2013-02356160, Ricerca Corrente ‘Neuroscienze Sperimentali’ and 5x1000 Anno 2016 to Fondazione Santa Lucia).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent for research purposes and for the publication of this study was obtained from the family described in this report.

Supplementary material

11033_2019_5109_MOESM1_ESM.docx (203 kb)
Supplementary material 1 (DOCX 202 kb)


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Neurogenetics UnitIRCCS Fondazione Santa LuciaRomeItaly
  2. 2.Department of Molecular MedicineUniversity of PaviaPaviaItaly
  3. 3.IRCCS Stella Maris FoundationPisaItaly
  4. 4.Department of Clinical and Experimental MedicineUniversity of PisaPisaItaly
  5. 5.Department of Medicine and SurgeryUniversity of SalernoSalernoItaly
  6. 6.Department of Neuroscience, Biomedicine, Movement-Neurology (Child Neurology and Psychiatry, and Neuropathology)University of VeronaVeronaItaly
  7. 7.Laboratory of Medical GeneticsBambino Gesù Children’s HospitalRomeItaly
  8. 8.Unit of Child Neurology, IRCCS Policlinico Gemelli FoundationCatholic UniversityRomeItaly
  9. 9.IRCCS Mondino FoundationPaviaItaly

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