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. 2022 Apr:97:52-56.
doi: 10.1016/j.parkreldis.2022.03.007. Epub 2022 Mar 16.

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

Barbara Garavaglia  1 , Sadeq Vallian  2 , Luigi M Romito  3 , Giulia Straccia  3 , Marianna Capecci  4 , Federica Invernizzi  1 , Elisa Andrenelli  4 , Arezu Kazemi  2 , Sylvia Boesch  5 , Robert Kopajtich  6 , Nahid Olfati  7 , Mohammad Shariati  8 , Ali Shoeibi  9 , Ariane Sadr-Nabavi  10 , Holger Prokisch  6 , Juliane Winkelmann  11 , Michael Zech  12
Affiliations

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

Barbara Garavaglia et al. Parkinsonism Relat Disord. 2022 Apr.

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.

Keywords: AOPEP variants; Dystonia-parkinsonism; Exome sequencing; Isolated dystonia; Recessive dystonia.

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