期刊
PARKINSONISM & RELATED DISORDERS
卷 97, 期 -, 页码 52-56出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.parkreldis.2022.03.007
关键词
Recessive dystonia; Isolated dystonia; Dystonia-parkinsonism; Exome sequencing; AOPEP variants
资金
- Technische Universitat Muenchen, Munich, Germany
- Helmholtz Zentrum Muenchen, Munich, Germany [DFG 458949627, ZE 1213/2-1, WI 1820/14-1]
- European Reference Network for Rare Neurological Diseases [739510]
- German Research Foundation [DFG 458949627, ZE 1213/2-1, WI 1820/14-1]
- [P09]
This study reports the role of AOPEP gene in recessive forms of generalized dystonia and dystonia-parkinsonism, suggesting that AOPEP variants are a major cause of dystonic movement-disorder phenotypes worldwide.
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.
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