Biallelic AOPEP Loss‐of‐Function Variants Cause Progressive Dystonia with Prominent Limb Involvement

Abstract

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Expanded Genetic Spectrum and Variable Disease Onset in AOPEP‐Associated Dystonia

“…7 No other de novo class IV or V variant was identified in this cohort. The TMEM151A mutation was identified in one of 23 patients of our PRRT2negative PKD cohort, which is in accordance with the frequency of 4.8% found by Tian et al 1 We report on a de novo mutation in TMEM151A in a patient with PKD. Our findings confirm TMEM151A variants as a genetic cause of PKD and suggest that de novo mutations in this gene are infrequently responsible for…”

“…An athetotic component was observed as well. Similarly to proband 3 reported by Zech et al, 1 carrying the identical p.Ala234Serfs*5 change in a homozygous state, he reported that dystonia improved when he had time to relax with symptoms completely subsiding. By sitting with the back against the wall, the retrocollis could be antagonized.…”

“…We read with great interest the article by Tian and colleagues. 1 Heterozygous mutations in TMEM151A, encoding transmembrane protein 151 A, a protein of undetermined function, have been very recently associated with paroxysmal kinesigenic dyskinesia (PKD) in the Chinese population. [1][2][3][4] TMEM151A is highly expressed in the brain, including the cerebral cortex and the thalamus and is highly conserved among species.…”

“…1 Heterozygous mutations in TMEM151A, encoding transmembrane protein 151 A, a protein of undetermined function, have been very recently associated with paroxysmal kinesigenic dyskinesia (PKD) in the Chinese population. [1][2][3][4] TMEM151A is highly expressed in the brain, including the cerebral cortex and the thalamus and is highly conserved among species. To definitively confirm the association between TMEM151A and PKD, other mutations in the same gene should be identified in independent cohorts from different populations.…”

Classification of Dystonia

“…The disease course is progressive and speech articulation difficulties, muscle cramping and pain, orofacial dyskinesia, and swallowing dysfunction were described. In a French family, late onset parkinsonism with prominent bradikynesia, dysarthria, and frequent falls was described [117].…”