1. AOPEP variants as a novel cause of recessive dystonia: Generalized dystonia and dystonia-parkinsonism.
- Author
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Garavaglia, Barbara, Vallian, Sadeq, Romito, Luigi M., Straccia, Giulia, Capecci, Marianna, Invernizzi, Federica, Andrenelli, Elisa, Kazemi, Arezu, Boesch, Sylvia, Kopajtich, Robert, Olfati, Nahid, Shariati, Mohammad, Shoeibi, Ali, Sadr-Nabavi, Ariane, Prokisch, Holger, Winkelmann, Juliane, and Zech, Michael
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GENETIC mutation , *DYSTONIA , *PARKINSONIAN disorders , *GENETIC techniques , *GENEALOGY - 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. [ABSTRACT FROM AUTHOR]- Published
- 2022
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