{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T16:13:44Z","timestamp":1783527224215,"version":"3.55.0"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Science and Technology Development Program of Jinan Municipal Health Commission","award":["2024304026"],"award-info":[{"award-number":["2024304026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dual molecular diagnoses involving concurrent monogenic variants and imprinting disorders are increasingly recognized in complex phenotypes, yet systematic approaches to elucidate such convergence remain limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We report a 46,XY proband with disorders of sex development (DSD), global developmental delay, and clinical features suggestive of Prader\u2013Willi syndrome (PWS). We performed whole-exome sequencing (WES) to identify sequence-level variants. Upon detection of copy-neutral loss of heterozygosity (CN-LOH), we used methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) to assess imprinting status and performed single-nucleotide polymorphism (SNP) microarray to characterize the extent and allelic architecture.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>WES identified a maternally inherited heterozygous deletion spanning exons 2\u20137 of NR5A1, classified as likely pathogenic based on its predicted loss-of-function impact on this dosage-sensitive transcription factor. WES also detected a 13.95\u00a0Mb CN-LOH at 15q21.1q21.3. MS-MLPA revealed a methylation profile consistent with maternal uniparental disomy of chromosome 15 (UPD(15)), confirming PWS. SNP microarray detected a larger 32.7\u00a0Mb CN-LOH across 15q14\u2013q21.3. The combined data support maternal UPD(15) involving mixed heterodisomy and isodisomy, likely arising from meiotic nondisjunction followed by trisomy rescue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>An integrated genomic strategy resolved dual etiologies\u2014NR5A1 haploinsufficiency and maternal UPD(15)\u2014underlying complex neurodevelopmental and reproductive features. Demonstrating how integrated analysis of sequence variation, epigenetic regulation, and genome-wide allelic architecture can uncover coexisting monogenic and imprinting mechanisms, this case highlights a diagnostic strategy warranting further evaluation in broader cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/hmg\/ddag055","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:16:15Z","timestamp":1783523775000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrated multi-platform genetic profiling reveals dual molecular pathology in 46, XY disorders of sex development through\n                    <i>NR5A1<\/i>\n                    Haploinsufficiency and maternal chromosome 15 UPD"],"prefix":"10.1093","volume":"35","author":[{"given":"Rui","family":"Dong","sequence":"first","affiliation":[{"name":"Department of pediatrics, Children's Hospital Affiliated to Shandong University (Jinan Children\u2019s Hospital) , No. 23976 Jingshi Road, Huaiyin District, Jinan, 250022 ,","place":["China"]},{"name":"Shandong Provincial Clinical Research Center for Children\u2019s Health and Disease, Children's Hospital Affiliated to Shandong University, No. 23976 Jingshi Road, Huaiyin District , Jinan, 250022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of pediatrics, Children's Hospital Affiliated to Shandong University (Jinan Children\u2019s Hospital) , No. 23976 Jingshi Road, Huaiyin District, Jinan, 250022 ,","place":["China"]},{"name":"Shandong Provincial Clinical Research Center for Children\u2019s Health and Disease, Children's Hospital Affiliated to Shandong University, No. 23976 Jingshi Road, Huaiyin District , Jinan, 250022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of pediatrics, Children's Hospital Affiliated to Shandong University (Jinan Children\u2019s Hospital) , No. 23976 Jingshi Road, Huaiyin District, Jinan, 250022 ,","place":["China"]},{"name":"Shandong Provincial Clinical Research Center for Children\u2019s Health and Disease, Children's Hospital Affiliated to Shandong University, No. 23976 Jingshi Road, Huaiyin District , Jinan, 250022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunkun","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of pediatrics, Children's Hospital Affiliated to Shandong University (Jinan Children\u2019s Hospital) , No. 23976 Jingshi Road, Huaiyin District, Jinan, 250022 ,","place":["China"]},{"name":"Shandong Provincial Clinical Research Center for Children\u2019s Health and Disease, Children's Hospital Affiliated to Shandong University, No. 23976 Jingshi Road, Huaiyin District , Jinan, 250022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of pediatrics, Children's Hospital Affiliated to Shandong University (Jinan Children\u2019s Hospital) , No. 23976 Jingshi Road, Huaiyin District, Jinan, 250022 ,","place":["China"]},{"name":"Shandong Provincial Clinical Research Center for Children\u2019s Health and Disease, Children's Hospital Affiliated to Shandong University, No. 23976 Jingshi Road, Huaiyin District , Jinan, 250022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0797-5171","authenticated-orcid":false,"given":"Xiaochen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of pediatrics, Children's Hospital Affiliated to Shandong University (Jinan Children\u2019s Hospital) , No. 23976 Jingshi Road, Huaiyin District, Jinan, 250022 ,","place":["China"]},{"name":"Shandong Provincial Clinical Research Center for Children\u2019s Health and Disease, Children's Hospital Affiliated to Shandong University, No. 23976 Jingshi Road, Huaiyin District , Jinan, 250022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaisheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of pediatrics, Children's Hospital Affiliated to Shandong University (Jinan Children\u2019s Hospital) , No. 23976 Jingshi Road, Huaiyin District, Jinan, 250022 ,","place":["China"]},{"name":"Shandong Provincial Clinical Research Center for Children\u2019s Health and Disease, Children's Hospital Affiliated to Shandong University, No. 23976 Jingshi Road, Huaiyin District , Jinan, 250022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of pediatrics, Children's Hospital Affiliated to Shandong University (Jinan Children\u2019s Hospital) , No. 23976 Jingshi Road, Huaiyin District, Jinan, 250022 ,","place":["China"]},{"name":"Shandong Provincial Clinical Research Center for Children\u2019s Health and Disease, Children's Hospital Affiliated to Shandong University, No. 23976 Jingshi Road, Huaiyin District , Jinan, 250022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4799-9133","authenticated-orcid":false,"given":"Kaihui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of pediatrics, Children's Hospital Affiliated to Shandong University (Jinan Children\u2019s Hospital) , No. 23976 Jingshi Road, Huaiyin District, Jinan, 250022 ,","place":["China"]},{"name":"Shandong Provincial Clinical Research Center for Children\u2019s Health and Disease, Children's Hospital Affiliated to Shandong University, No. 23976 Jingshi Road, Huaiyin District , Jinan, 250022 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