Dominant <scp><i>VPS16</i></scp> Pathogenic Variants: Not Only Isolated Dystonia-Reference-Cited by-同舟云学术

Dominant VPS16 Pathogenic Variants: Not Only Isolated Dystonia

Published:2023-12-12 Issue:1 Volume:11 Page:87-93
ISSN:2330-1619
Container-title:Movement Disorders Clinical Practice
language:en
Short-container-title:Movement Disord Clin Pract

Author:

Monfrini Edoardo¹²^ORCID,Avanzino Laura³⁴^ORCID,Palermo Giovanni⁵,Bonato Giulia⁶,Brescia Gloria¹⁷,Ceravolo Roberto⁵,Cantarella Giovanna⁸⁹,Mandich Paola⁴¹⁰,Prokisch Holger¹¹¹²,Storm van's Gravesande Karin¹³¹⁴,Straccia Giulia¹⁵,Elia Antonio¹⁵,Reale Chiara¹⁶,Panteghini Celeste¹⁶,Zorzi Giovanna¹⁷^ORCID,Eleopra Roberto¹⁵,Erro Roberto¹⁸^ORCID,Carecchio Miryam⁵,Garavaglia Barbara¹⁶,Zech Michael¹¹¹²¹⁹^ORCID,Romito Luigi¹⁵^ORCID,Di Fonzo Alessio²^ORCID

Affiliation:

1. Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation University of Milan Milan Italy

2. Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico Neurology Unit Milan Italy

3. Department of Experimental Medicine, Section of Human Physiology and Centro Polifunzionale di Scienze Motorie University of Genoa Genoa Italy

4. IRCCS Ospedale Policlinico San Martino Genoa Italy

5. Center for Neurodegenerative Diseases, Parkinson's Disease and Movement Disorders, Unit of Neurology, Department of Clinical and Experimental Medicine University of Pisa Pisa Italy

6. Parkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases (ERN‐RND), Department of Neuroscience University of Padua Padua Italy

7. Medical Genetics Laboratory Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milan Italy

8. Department of Clinical Sciences and Community Health University of Milan Milan Italy

9. Department of Otolaryngology Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milan Italy

10. Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal, and Child Health University of Genoa Genoa Italy

11. Institute of Neurogenomics, Helmholtz Munich Neuherberg Germany

12. Institute of Human Genetics, Technical University of Munich, School of Medicine Munich Germany

13. Department of Pediatrics, Child and Adolescent Psychosomatics Technical University Munich Munich Germany

14. Department of Pediatric Neurology University Children's Hospital Freiburg Freiburg Germany

15. Department of Clinical Neurosciences, Parkinson and Movement Disorders Unit Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy

16. Medical Genetics and Neurogenetics Unit Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy

17. Department of Pediatric Neuroscience Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy

18. Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana,” Neuroscience Section University of Salerno Salerno Italy

19. Institute for Advanced Study, Technical University of Munich Garching Germany

Abstract

AbstractBackgroundVPS16 pathogenic variants have been recently associated with inherited dystonia. Most patients affected by dominant VPS16‐related disease display early‐onset isolated dystonia with prominent oromandibular, bulbar, cervical, and upper limb involvement, followed by slowly progressive generalization.CasesWe describe six newly reported dystonic patients carrying VPS16 mutations displaying unusual phenotypic features in addition to dystonia, such as myoclonus, choreoathetosis, pharyngospasm and freezing of gait. Response to bilateral Globus Pallidus Internus Deep Brain Stimulation (GPi‐DBS) is reported in three of them, associated with significant improvement of dystonia but only minor effect on other hyperkinetic movements. Moreover, five novel pathogenic/likely pathogenic variants are described.ConclusionsThis case collection expands the genetic and clinical spectrum of VPS16‐related disease, prompting movement disorder specialists to suspect mutations of this gene not only in patients with isolated dystonia.

Funder

Fondazione Regionale per la Ricerca Biomedica

Ministero della Salute

Publisher

Wiley

Subject

Neurology (clinical),Neurology

Reference10 articles.

1. Loss‐of‐Function Variants in HOPS Complex Genes VPS16 and VPS41 Cause Early Onset Dystonia Associated with Lysosomal Abnormalities

2. Homozygous mutation of VPS16 gene is responsible for an autosomal recessive adolescent-onset primary dystonia

3. HOPS-associated neurological disorders (HOPSANDs): linking endolysosomal dysfunction to the pathogenesis of dystonia

4. Truncating VPS16 Mutations Are Rare in Early Onset Dystonia

5. A Recurrent VPS16 p.Arg187* Nonsense Variant in Early‐Onset Generalized Dystonia