{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T13:30:17Z","timestamp":1787923817896,"version":"build-2784847793"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the molecular etiology in a male child clinically suspected of congenital adrenal hyperplasia (CAH) with negative conventional genetic testing, and to elucidate the genetic characteristics of his pedigree.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Clinical data from the proband and his family members were collected. Molecular diagnostics proceeded sequentially: initial targeted CAH testing (\n                      <jats:italic>CYP21A2<\/jats:italic>\n                      and\n                      <jats:italic>POR<\/jats:italic>\n                      sequencing\/MLPA, plus targeted\n                      <jats:italic>NR0B1<\/jats:italic>\n                      CNV analysis) was followed by whole-exome sequencing coupled with genome-wide CNV analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The proband presented with neonatal cyanosis and hyperpigmentation. Laboratory tests showed markedly elevated ACTH (354.68 pmol\/L) and low aldosterone (57.24 pg\/mL). Molecular genetic testing identified a hemizygous deletion of approximately 4.44 Mb at Xp21.3-p21.1 (chrX:g.27080000_31520000), encompassing the\n                      <jats:italic>NR0B1<\/jats:italic>\n                      ,\n                      <jats:italic>GK<\/jats:italic>\n                      ,\n                      <jats:italic>IL1RAPL1<\/jats:italic>\n                      , and\n                      <jats:italic>DMD<\/jats:italic>\n                      genes. CNV-seq confirmed that the mother carried a heterozygous deletion of 4.38 Mb in the same region, while the father and four maternal aunts showed normal genotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study ultimately diagnosed the proband with Xp21 contiguous gene deletion syndrome. The adrenal insufficiency resulted from X-linked congenital adrenal hypoplasia (AHC) due to\n                      <jats:italic>NR0B1<\/jats:italic>\n                      haploinsufficiency, rather than CAH. These findings highlight the considerable clinical overlap between AHC and CAH, indicating that CNV analysis of the Xp21 region should be included in the diagnostic workup for male infants with suspected CAH but negative routine genetic testing. This provides a basis for the precise diagnosis and genetic counseling of such patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1883655","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:51:30Z","timestamp":1787921490000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Xp21 contiguous gene deletion syndrome presenting as congenital adrenal hypoplasia: molecular diagnosis and clinical re-evaluation of a pedigree"],"prefix":"10.3389","volume":"17","author":[{"given":"Donghua","family":"Zhang","sequence":"first","affiliation":[{"name":"Yulin Women and Children Health Care Hospital","place":["Yulin, Guangxi Zhuang Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchun","family":"Li","sequence":"additional","affiliation":[{"name":"Yulin Women and Children Health Care Hospital","place":["Yulin, Guangxi Zhuang Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Li","sequence":"additional","affiliation":[{"name":"Yulin Women and Children Health Care Hospital","place":["Yulin, Guangxi Zhuang Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghong","family":"Lu","sequence":"additional","affiliation":[{"name":"Yulin Women and Children Health Care Hospital","place":["Yulin, Guangxi Zhuang Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sisi","family":"Ning","sequence":"additional","affiliation":[{"name":"Yulin Women and Children Health Care Hospital","place":["Yulin, Guangxi Zhuang Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiafei","family":"Liang","sequence":"additional","affiliation":[{"name":"Yulin Women and Children Health Care Hospital","place":["Yulin, Guangxi 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