{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T23:20:35Z","timestamp":1793748035960,"version":"4.6.1"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T00:00:00Z","timestamp":1667865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>We present a patient with unusual episodes of muscular weakness due to homozygous deletion of exon 2 in the <jats:italic>MICU1<\/jats:italic> gene. Forty-three patients from 33 families were previously described with homozygous and compound heterozygous, predominantly loss of function (LoF) variants in the <jats:italic>MICU1<\/jats:italic> gene that lead to autosomal recessive myopathy with extrapyramidal signs. Most described patients developed muscle weakness and elevated CK levels, and half of the patients had progressive extrapyramidal signs and learning disabilities. Our patient had a few severe acute episodes of muscle weakness with minimal myopathy features between episodes and a strongly elevated Creatinine Kinase (CK). Whole exome sequencing (WES) was performed and the homozygous deletion of exon 2 was suspected. To validate the diagnosis, we performed an RNA analysis of all family members. To investigate the possible impact of this deletion on the phenotype, we predicted a new Kozak sequence in exon 4 that could lead to the formation of a truncated MICU1 protein that could partly interact with MCU protein in a mitochondrial Ca<jats:sup>2+<\/jats:sup> complex. We suspect that this unusual phenotype of the proband with MICU1-related myopathy could be explained by the presence of the truncated but partly functional protein. This work helps to define the clinical polymorphism of <jats:italic>MICU1<\/jats:italic> deficiency better.<\/jats:p>","DOI":"10.3389\/fneur.2022.1008937","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T05:49:05Z","timestamp":1667886545000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Case report: Unusual episodic myopathy in a patient with novel homozygous deletion of first coding exon of MICU1 gene"],"prefix":"10.3389","volume":"13","author":[{"given":"Margarita","family":"Sharova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Skoblov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Dadali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Demina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Shchagina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fedor","family":"Konovalov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ampleeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna","family":"Sharkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Kutsev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1038\/nature10230","article-title":"forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter","volume":"476","author":"De Stefani","year":"2011","journal-title":"Nature."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1038\/ncb2622","article-title":"MCUR1 is an essential component of mitochondrial Ca2+ uptake that regulates cellular metabolism","volume":"14","author":"Mallilankaraman","year":"2012","journal-title":"Nat Cell Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/j.cell.2012.10.011","article-title":"MICU1 is an essential gatekeeper for mcu-mediated mitochondrial Ca2+ uptake that regulates cell survival","volume":"151","author":"Mallilankaraman","year":"2012","journal-title":"Cell."},{"key":"B4","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/nature09358","article-title":"MICU1 encodes a mitochondrial EF hand protein required for Ca2+ uptake","volume":"467","author":"Perocchi","year":"2010","journal-title":"Nature."},{"key":"B5","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1038\/ng.2851","article-title":"Loss-of-function mutations in MICU1 cause a brain and muscle disorder linked to primary alterations in mitochondrial calcium signaling","volume":"46","author":"Logan","year":"2014","journal-title":"Nat Genet."},{"key":"B6","first-page":"79","volume-title":"A middle eastern founder mutation expands the genotypic and phenotypic spectrum of mitochondrial MICU1 deficiency: A report of 13 patients. 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