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This study uses next\u2010generation sequencing (NGS) and long\u2010read sequencing data (LRS) in Chinese AR\u2010PD families to uncover novel genes, enhancing our genetic comprehension of PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated 162 AR\u2010PD families and 1570 sporadic early\u2010onset PD patients, combining homozygous mapping and whole\u2010exome sequencing (WES) to identify candidates. Using the GenoPriori\u2010WeightSchem approach, we conducted population\u2010based prioritization of candidate genes. We prioritized biallelic loss\u2010of\u2010function variants in the candidate gene pool. LRS dataset were analyzed to investigate genes with structural genomic variants. The identified candidates were further validated in 3947 PD cases from our in\u2010house whole\u2010genome sequencing (WGS) dataset, along with 3100 PD cases derived from the UK Biobank WES dataset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Analysis of WES data from 25 core AR\u2010PD families revealed five candidate genes:\n                      <jats:italic>ROBO1<\/jats:italic>\n                      ,\n                      <jats:italic>LMBR1L<\/jats:italic>\n                      ,\n                      <jats:italic>RIOX2<\/jats:italic>\n                      ,\n                      <jats:italic>INTS2<\/jats:italic>\n                      , and\n                      <jats:italic>H6PD<\/jats:italic>\n                      . The GenoPriori\u2010WeightSchem approach highlighted an additional five candidate genes:\n                      <jats:italic>SORL1<\/jats:italic>\n                      ,\n                      <jats:italic>PSD2<\/jats:italic>\n                      ,\n                      <jats:italic>BRD9<\/jats:italic>\n                      ,\n                      <jats:italic>EPG5<\/jats:italic>\n                      , and\n                      <jats:italic>SH3PXD2A<\/jats:italic>\n                      . Focusing on homozygous loss\u2010of\u2010function variants, indicative of severe genetic impact, we identified six genes in AR\u2010PD families:\n                      <jats:italic>LRPPRC<\/jats:italic>\n                      ,\n                      <jats:italic>PPP1R1B<\/jats:italic>\n                      ,\n                      <jats:italic>C1RL<\/jats:italic>\n                      ,\n                      <jats:italic>LNPK<\/jats:italic>\n                      ,\n                      <jats:italic>HSD11B1L<\/jats:italic>\n                      , and\n                      <jats:italic>PPP1R3E<\/jats:italic>\n                      . LRS data from 38 families revealed a homozygous structure variant, a 6.3\u2009kb deletion, in the\n                      <jats:italic>COL24A1<\/jats:italic>\n                      gene. Finally, eight of the identified candidate genes were consistently associated with PD in two independent replication stages.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study identified eight promising candidate genes using a large sample of AR\u2010PD families, combining NGS and LRS data, which may expand the spectrum of candidate autosomal recessive genes responsible for PD. \u00a9 2025 International Parkinson and Movement Disorder Society.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70039","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T09:37:24Z","timestamp":1758101844000},"page":"2770-2781","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Expanding the Autosomal Recessive Gene Spectrum of Parkinson's Disease: A 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