{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T13:31:45Z","timestamp":1781703105622,"version":"3.54.5"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"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><jats:title>Objective<\/jats:title><jats:p>To determine the genetic etiology of a family pedigree with two patients affected by differences of sex development (DSD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Assess the clinical characteristics of the patients and achieve exome sequencing results and <jats:italic>in vitro<\/jats:italic> functional studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The 15-year-old proband, raised as female, presented with delayed puberty and short stature associated with atypical genitalia. Hormonal profile showed hypergonadotrophic hypogonadism. Imaging studies revealed the absence of a uterus and ovaries. The karyotype confirmed a 46, XY pattern. Her younger brother presented with a micropenis and hypoplastic scrotum with non-palpable testis and hypospadias. Laparoscopic exploration was performed on the younger brother. Streak gonads were found and removed due to the risk of neoplastic transformation. Post-operative histopathology showed the co-existence of Wolffian and M\u00fcllerian derivatives. Whole-exome sequencing identified a novel mutation (c.1223C&amp;gt;T, p. Ser408Leu) in the Asp-Glu-Ala-His-box helicase 37 gene, which was found to be deleterious by <jats:italic>in silico<\/jats:italic> analysis. Segregation analysis of the variant displayed a sex-limited, autosomal dominant, maternal inheritance pattern. <jats:italic>In vitro<\/jats:italic> experiments revealed that the substitution of 408Ser by Leu caused decreased DHX37 expression both at the mRNA and protein levels. Moreover, the \u03b2-catenin protein was upregulated, and the p53 protein was unaltered by mutant <jats:italic>DHX37<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We described a novel mutation (c.1223C&amp;gt;T, p. Ser408Leu) of the <jats:italic>DHX37<\/jats:italic> gene associated with a Chinese pedigree consisting of two 46, XY DSD patients. We speculated that the underlying molecular mechanism might involve upregulation of the \u03b2-catenin protein.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1059159","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T13:00:51Z","timestamp":1680181251000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["A novel DEAH-box helicase 37 mutation associated with differences of sex development"],"prefix":"10.3389","volume":"14","author":[{"given":"Yun","family":"Wan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richeng","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingju","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2006-0738","article-title":"Consensus statement on management of intersex disorders. 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