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We previously identified a 7 megabases complex structural variant in a pair of monozygotic twins using Oxford Nanopore Technologies (ONT) long\u2010read sequencing. This study aims to determine if ONT long\u2010read sequencing can detect a second variant in other unresolved early\u2010onset Parkinson's disease (EOPD) cases with 1 heterozygous PRKN<\/jats:italic> or PINK1<\/jats:italic> variant.<\/jats:p><\/jats:sec>Methods<\/jats:title>ONT long\u2010read sequencing was performed on EOPD patients with 1 reported PRKN<\/jats:italic>\/PINK1<\/jats:italic> pathogenic variant, with onset age under 50. Positive controls included EOPD patients with 2 known PRKN<\/jats:italic> pathogenic variants. Initial testing involved short\u2010read targeted panel sequencing for single nucleotide variants and multiplex ligation\u2010dependent probe amplification for copy number variants.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 47 patients were studied (PRKN<\/jats:italic> \u201cone\u2010variant,\u201d n\u2009=\u200923; PINK1<\/jats:italic> \u201cone\u2010variant,\u201d n\u2009=\u200912; PRKN<\/jats:italic> \u201ctwo\u2010variants,\u201d n\u2009=\u200912). ONT long\u2010read sequencing identified a second pathogenic variant in 26% of PRKN<\/jats:italic> \u201cone\u2010variant\u201d patients (6\/23), but none in PINK1<\/jats:italic> \u201cone\u2010variant\u201d patients (0\/12). Detected variants included 1 complex inversion, 2 structural variant overlaps, and 3 duplications. In the PRKN<\/jats:italic> \u201ctwo\u2010variants\u201d group, both variants were identified in all patients (100%, 12\/12).<\/jats:p><\/jats:sec>Interpretation<\/jats:title>ONT long\u2010read sequencing effectively identifies pathogenic structural variants in the PRKN<\/jats:italic> locus missed by conventional methods. It should be considered for unresolved EOPD cases when a second variant is not detected through conventional approaches. 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