1. AOPEP variants as a novel cause of recessive dystonia: Generalized dystonia and dystonia-parkinsonism
- Author
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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, and Michael Zech
- Subjects
Dystonia ,Neurology ,Parkinsonian Disorders ,Dystonic Disorders ,Mutation ,Humans ,Neurology (clinical) ,Geriatrics and Gerontology ,Iran ,Child ,Aminopeptidases ,Pedigree - Abstract
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.1917-1GA essential splice-site variant and featured presentations of adolescence-onset generalized dystonia. An individual of Chinese descent, homozygous for the nonsense variant c.1909GT (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.1201CT [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.
- Published
- 2022