{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:25:18Z","timestamp":1788452718955,"version":"build-2803163510"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":28,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Facioscapulohumeral muscular dystrophy (FSHD) is caused by aberrant expression of the double homeobox transcription factor DUX4 in skeletal muscle. Because direct measurement of DUX4 in FSHD muscle is technically challenging, DUX4-regulated transcripts in muscle biopsies have been used as surrogates; however, this approach is invasive, limited to a single muscle, and less suitable for repeated monitoring. Thus, we sought to identify DUX4-regulated circulating biomarkers that could integrate DUX4 activity across all affected muscles and enable more frequent measurement. We performed mass spectrometry on conditioned media from DUX4-inducible immortalized human myoblasts (MB135iDUX4) and identified a top candidate\u2014KHDC1L, the protein product of a DUX4-regulated mRNA previously shown to correlate with DUX4 expression in muscle. Western blotting confirmed KHDC1L release into the supernatant of DUX4-expressing cells. Plasma profiling demonstrated elevated KHDC1L levels in individuals with FSHD compared to healthy controls, supporting its role as a circulating readout of DUX4 activity. These findings suggest that plasma KHDC1L is a potential pharmacodynamic marker of DUX4 activity, providing a minimally invasive tool for disease monitoring and a potential response marker to evaluate emerging FSHD therapies.<\/jats:p>","DOI":"10.1093\/hmg\/ddaf183","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T13:10:55Z","timestamp":1764162655000},"source":"Crossref","is-referenced-by-count":6,"title":["Identification of KHDC1L, a DUX4-regulated protein, as a novel plasma biomarker in facioscapulohumeral muscular dystrophy"],"prefix":"10.1093","volume":"35","author":[{"given":"Nicholas A","family":"Sutliff","sequence":"first","affiliation":[{"name":"Fred Hutchinson Cancer Center, Human Biology Division , 1100 Fairview Ave N, Seattle, WA 98109 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Chao","sequence":"additional","affiliation":[{"name":"Avidity Biosciences , 3020 Callan Rd, San Diego, CA 92121 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean R","family":"Bennett","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center, Human Biology Division , 1100 Fairview Ave N, Seattle, WA 98109 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee","family":"Nip","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center, Human Biology Division , 1100 Fairview Ave N, Seattle, WA 98109 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Lakhdari","sequence":"additional","affiliation":[{"name":"Avidity Biosciences , 3020 Callan Rd, San Diego, CA 92121 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Canton","sequence":"additional","affiliation":[{"name":"Avidity Biosciences , 3020 Callan Rd, San Diego, CA 92121 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Zhu","sequence":"additional","affiliation":[{"name":"Avidity Biosciences , 3020 Callan Rd, San Diego, CA 92121 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0319-0968","authenticated-orcid":false,"given":"Stephen J","family":"Tapscott","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center, Human Biology Division , 1100 Fairview Ave N, Seattle, WA 98109 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"2026051101314754100_ref1","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1212\/WNL.0000000000000797","article-title":"Population-based incidence and prevalence of facioscapulohumeral 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