{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:32:33Z","timestamp":1768566753138,"version":"3.49.0"},"posted":{"date-parts":[[2024,5,3]]},"group-title":"Neurology","reference-count":24,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,5,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    <jats:italic>PRKN<\/jats:italic>\n                    biallelic pathogenic variants are the most common cause of autosomal recessive early-onset Parkinson\u2019s disease (PD). However, the variants responsible for suspected\n                    <jats:italic>PRKN-<\/jats:italic>\n                    PD individuals are not always identified with standard genetic testing.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>\n                    Identify the genetic cause in two siblings with a\n                    <jats:italic>PRKN<\/jats:italic>\n                    -PD phenotype using long-read sequencing (LRS).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The genetic investigation involved standard testing using successively multiple ligation probe amplification (MLPA), Sanger sequencing, targeted sequencing, whole-exome sequencing and LRS.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    MLPA and targeted sequencing identified one copy of exon four in\n                    <jats:italic>PRKN<\/jats:italic>\n                    but no other variants were identified. Subsequently, LRS unveiled a large deletion encompassing exon 3 to 4 on one allele and a duplication of exon 3 on the second allele; explaining the siblings\u2019 phenotype. MLPA could not identify the balanced rearrangement of exon 3.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    This study highlights the potential utility of long-read sequencing in the context of unsolved typical\n                    <jats:italic>PRKN-<\/jats:italic>\n                    PD individuals.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.05.02.24306523","type":"posted-content","created":{"date-parts":[[2024,5,4]],"date-time":"2024-05-04T02:20:19Z","timestamp":1714789219000},"source":"Crossref","is-referenced-by-count":1,"title":["Long-read sequencing unravels the complexity of structural variants in\n                  <i>PRKN<\/i>\n                  in two individuals with early-onset Parkinson\u2019s disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3505-7114","authenticated-orcid":false,"given":"Guillaume","family":"Cogan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9177-9587","authenticated-orcid":false,"given":"Kensuke","family":"Daida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8003-4029","authenticated-orcid":false,"given":"Kimberley 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