AOPEP variants as a novel cause of recessive dystonia: Generalized dystonia and dystonia-parkinsonism

Barbara Garavaglia, Sadeq Vallian, Luigi M. Romito, Giulia Straccia, Marianna Capecci, Federica Invernizzi, Elisa Andrenelli, Arezu Kazemi, Sylvia Boesch, Robert Kopajtich, Nahid Olfati, Mohammad Shariati, Ali Shoeibi, Ariane Sadr-Nabavi, Holger Prokisch, Juliane Winkelmann, Michael Zech

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Introduction: The genetic basis of autosomal-recessive dystonia remains poorly understood. Our objective was to report identification of additional individuals with variants in AOPEP, a recently described gene for recessively inherited dystonic disorders (OMIM:619565). Methods: Ongoing analysis on a high-throughput genetic platform and international case-recruitment efforts were undertaken. Results: Novel biallelic, likely pathogenic loss-of-function alleles were identified in two pedigrees of different ethnic background. Two members of a consanguineous Iranian family shared a homozygous c.1917-1G>A essential splice-site variant and featured presentations of adolescence-onset generalized dystonia. An individual of Chinese descent, homozygous for the nonsense variant c.1909G>T (p.Glu637*), displayed childhood-onset generalized dystonia combined with later-manifesting parkinsonism. One additional Iranian patient with adolescence-onset generalized dystonia carried an ultrarare, likely protein-damaging homozygous missense variant (c.1201C>T [p.Arg401Trp]). Conclusions: These findings support the implication of AOPEP in recessive forms of generalized dystonia and dystonia-parkinsonism. Biallelic AOPEP variants represent a worldwide cause of dystonic movement-disorder phenotypes and should be considered in dystonia molecular testing approaches.

Original languageEnglish
Pages (from-to)52-56
Number of pages5
JournalParkinsonism and Related Disorders
Volume97
DOIs
StatePublished - Apr 2022

Keywords

  • AOPEP variants
  • Dystonia-parkinsonism
  • Exome sequencing
  • Isolated dystonia
  • Recessive dystonia

Fingerprint

Dive into the research topics of 'AOPEP variants as a novel cause of recessive dystonia: Generalized dystonia and dystonia-parkinsonism'. Together they form a unique fingerprint.

Cite this