{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:39:55Z","timestamp":1792640395621,"version":"4.5.0"},"reference-count":44,"publisher":"BMJ","issue":"11","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["8237061071"],"award-info":[{"award-number":["8237061071"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2022YFC2703400"],"award-info":[{"award-number":["2022YFC2703400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2025,7,16]]},"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Facioscapulohumeral muscular dystrophy 1 (FSHD1) is one of the most common autosomal dominant neuromuscular diseases. Genetic diagnosis of FSHD1 remains a challenge because of the long length and repetitive nature of D4Z4 repeats. Long-read sequencing is an effective method for detecting FSHD1, but sequencing depth remains a limitation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a long-read library adaptive sampling (LRL-AS) method based on Oxford Nanopore Technologies (ONT) sequencing to comprehensively detect FSHD1. Two patients were sequenced by adaptive sampling, followed by analyses of D4Z4 repeat units (RUs), methylation and haplotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with whole-genome sequencing, our LRL-AS method shows significant improvements in both sequencing depth and read length. LRL-AS can identify D4Z4 RUs contraction with accuracy comparable to optical genome mapping in both 4q35 and 10q26 regions. We also calculated methylation levels in the double homeobox 4 (\n                      <jats:italic>DUX4<\/jats:italic>\n                      ) gene region. With the benefit of higher sequencing depth, allele-specific methylation can be calculated with greater precision. We also observed that, at different sequencing depths, ONT sequencing data consistently provide stable calculations of methylation levels. More importantly, we demonstrated that data from adaptive sampling can be effectively used to construct the haplotype of the pathogenic allele using single-nucleotide polymorphisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our LRL-AS method is a comprehensive approach for FSHD1 detection, improving the accuracy of D4Z4 RUs and methylation detection while enabling allele-specific haplotype construction. It holds promising potential for clinical application.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmg-2025-110827","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T05:45:11Z","timestamp":1753940711000},"page":"669-676","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Accurate detection of D4Z4 repeats, methylation and allele haplotype in facioscapulohumeral muscular dystrophy 1 using nanopore long-read adaptive sampling sequencing: a pilot study"],"prefix":"10.1136","volume":"62","author":[{"given":"Mingtao","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Prenatal Diagnosis, Women\u2019s Hospital of Nanjing Medical University, Nanjing Women and Children\u2019s Healthcare Hospital, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Prenatal Diagnosis, Women\u2019s Hospital of Nanjing Medical University, Nanjing Women and Children\u2019s Healthcare Hospital, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihui","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Prenatal Diagnosis, Women\u2019s Hospital of Nanjing Medical University, Nanjing Women and Children\u2019s Healthcare Hospital, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Prenatal Diagnosis, Women\u2019s Hospital of Nanjing Medical University, Nanjing Women and Children\u2019s Healthcare Hospital, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Prenatal Diagnosis, Women\u2019s Hospital of Nanjing Medical University, Nanjing Women and Children\u2019s Healthcare Hospital, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengfeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Prenatal Diagnosis, Women\u2019s Hospital of Nanjing Medical University, Nanjing Women and Children\u2019s Healthcare Hospital, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7297-8847","authenticated-orcid":false,"given":"Ping","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Prenatal Diagnosis, Women\u2019s Hospital of Nanjing Medical University, Nanjing Women and Children\u2019s Healthcare Hospital, Nanjing, Jiangsu, China"},{"name":"Jiangsu Provincial Key Laboratory of Biological Therapy for Organ Failure, Nanjing Medical University, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"2025102806151071000_62.11.669.1","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1212\/WNL.0000000000000797","article-title":"Population-based incidence and prevalence of facioscapulohumeral dystrophy","volume":"83","author":"Deenen","year":"2014","journal-title":"Neurology (ECronicon)"},{"key":"2025102806151071000_62.11.669.2","unstructured":"Preston MK , Tawil R , Wang LH . Facioscapulohumeral muscular dystrophy. In: Adam MP , Feldman J , Mirzaa GM , et al , eds. GeneReviews((R). 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