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

Parkinsonism & related disorders 2022 Apr

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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). Ongoing analysis on a high-throughput genetic platform and international case-recruitment efforts were undertaken. 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]). 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. Copyright © 2022 Elsevier Ltd. All rights reserved.

Citation

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. AOPEP variants as a novel cause of recessive dystonia: Generalized dystonia and dystonia-parkinsonism. Parkinsonism & related disorders. 2022 Apr;97:52-56