{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:42:00Z","timestamp":1760150520299,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T00:00:00Z","timestamp":1701216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondation Maladies Rares","award":["18-AOI-07"],"award-info":[{"award-number":["18-AOI-07"]}]},{"name":"AOI","award":["18-AOI-07"],"award-info":[{"award-number":["18-AOI-07"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Mitochondrial disorders are characterized by a huge clinical, biochemical, and genetic heterogeneity, which poses significant diagnostic challenges. Several studies report that more than 50% of patients with suspected mitochondrial disease could have a non-mitochondrial disorder. Thus, only the identification of the causative pathogenic variant can confirm the diagnosis. Herein, we describe the diagnostic journey of a family suspected of having a mitochondrial disorder who were referred to our Genetics Department. The proband presented with the association of cerebellar ataxia, COX-negative fibers on muscle histology, and mtDNA deletions. Whole exome sequencing (WES), supplemented by a high-resolution array, comparative genomic hybridization (array-CGH), allowed us to identify two pathogenic variants in the non-mitochondrial SYNE1 gene. The proband and her affected sister were found to be compound heterozygous for a known nonsense variant (c.13258C&gt;T, p.(Arg4420Ter)), and a large intragenic deletion that was predicted to result in a loss of function. To our knowledge, this is the first report of a large intragenic deletion of SYNE1 in patients with cerebellar ataxia (ARCA1). This report highlights the interest in a pangenomic approach to identify the genetic basis in heterogeneous neuromuscular patients with the possible cause of mitochondrial disease. Moreover, even rare copy number variations should be considered in patients with a phenotype suggestive of SYNE1 deficiency.<\/jats:p>","DOI":"10.3390\/genes14122154","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T03:48:24Z","timestamp":1701229704000},"page":"2154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Case Report of SYNE1 Deficiency-Mimicking Mitochondrial Disease and the Value of Pangenomic Investigations"],"prefix":"10.3390","volume":"14","author":[{"given":"Mounir","family":"Serag","sequence":"first","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital l\u2019Archet 2, CHU de Nice, 151 Route Saint-Antoine de Ginesti\u00e8re, 06202 Nice, France"},{"name":"CNRS UMR7284\/ INSERM U1081, Facult\u00e9 de M\u00e9decine, Universit\u00e9 C\u00f4te d\u2019Azur, 06107 Nice, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morgane","family":"Plutino","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital l\u2019Archet 2, CHU de Nice, 151 Route Saint-Antoine de Ginesti\u00e8re, 06202 Nice, France"},{"name":"CNRS UMR7284\/ INSERM U1081, Facult\u00e9 de M\u00e9decine, Universit\u00e9 C\u00f4te d\u2019Azur, 06107 Nice, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Perrine","family":"Charles","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, La Piti\u00e9-Salp\u00eatri\u00e8re, AP-HP, 75610 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Philippe","family":"Azulay","sequence":"additional","affiliation":[{"name":"Service de Neurologie, 13005 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annabelle","family":"Chaussenot","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital l\u2019Archet 2, CHU de Nice, 151 Route Saint-Antoine de Ginesti\u00e8re, 06202 Nice, France"},{"name":"CNRS UMR7284\/ INSERM U1081, Facult\u00e9 de M\u00e9decine, Universit\u00e9 C\u00f4te d\u2019Azur, 06107 Nice, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00e9ronique","family":"Paquis-Flucklinger","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital l\u2019Archet 2, CHU de Nice, 151 Route Saint-Antoine de Ginesti\u00e8re, 06202 Nice, France"},{"name":"CNRS UMR7284\/ INSERM U1081, Facult\u00e9 de M\u00e9decine, Universit\u00e9 C\u00f4te d\u2019Azur, 06107 Nice, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7204-7826","authenticated-orcid":false,"given":"Samira","family":"Ait-El-Mkadem Saadi","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital l\u2019Archet 2, CHU de Nice, 151 Route Saint-Antoine de Ginesti\u00e8re, 06202 Nice, France"},{"name":"CNRS UMR7284\/ INSERM U1081, Facult\u00e9 de M\u00e9decine, Universit\u00e9 C\u00f4te d\u2019Azur, 06107 Nice, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2969-1904","authenticated-orcid":false,"given":"C\u00e9cile","family":"Rouzier","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital l\u2019Archet 2, CHU de Nice, 151 Route Saint-Antoine de Ginesti\u00e8re, 06202 Nice, France"},{"name":"CNRS UMR7284\/ INSERM U1081, Facult\u00e9 de M\u00e9decine, Universit\u00e9 C\u00f4te d\u2019Azur, 06107 Nice, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16080","DOI":"10.1038\/nrdp.2016.80","article-title":"Mitochondrial Diseases","volume":"2","author":"Gorman","year":"2016","journal-title":"Nat. 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