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Segmental dystonia as the prominent phenotype resulting from a MICU1 splice variant in a new Indian case

Published:September 09, 2022DOI:https://doi.org/10.1016/j.parkreldis.2022.08.031
      The MICU1 gene encodes the mitochondrial calcium uptake 1 protein, an essential regulator of mitochondrial Ca2+ uptake and mitochondrial calcium homeostasis [
      • Debattisti V.
      • Horn A.
      • Singh R.
      • et al.
      Dysregulation of mitochondrial Ca2+ uptake and sarcolemma repair underlie muscle weakness and wasting in patients and mice lacking MICU1.
      ]. Bi-allelic loss-of-function (LOF) variants in MICU1 are known to cause a rare, autosomal recessive neuromuscular disease, also termed ‘myopathy with extrapyramidal signs’ (MPXPS) (OMIM #615673) [
      • Logan C.V.
      • Szabadkai G.
      • Sharpe J.A.
      • et al.
      Loss-of-function mutations in MICU1 cause a brain and muscle disorder linked to primary alterations in mitochondrial calcium signaling.
      ]. The clinical phenotype usually includes childhood-onset proximal weakness with increased serum CK and liver enzymes, developmental delay and intellectual disability. In some patients, movement disorders such as chorea and dystonia are reported at a later age. The previous literature has emphasized the muscle involvement in this disorder, while the dystonic features in most studies have not been outlined in detail (Supplementary Table 1). We herein describe our experience with a previously unreported Indian family with two siblings presenting with MPXPS, characterized by prominent segmental dystonia in the proband, and carrying a previously reported homozygous MICU1 splicing variant. The study procedures were approved by the local Institutional Board and participating subjects gave written informed consent.

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