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Targeted next\u2010generation and Sanger sequencing were performed to investigate pathogenic gene variants and validate<jats:italic><jats:styled-content style=\"fixed-case\">NR<\/jats:styled-content>5A1<\/jats:italic>gene variants, respectively. In silico tools and in vitro function studies were used to analyze the pathogenicity of rare variants. The clinical and endocrinological characteristics of patients with<jats:italic><jats:styled-content style=\"fixed-case\">NR<\/jats:styled-content>5A1<\/jats:italic>variants were retrospectively analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of four novel and three recurrent<jats:italic><jats:styled-content style=\"fixed-case\">NR<\/jats:styled-content>5A1<\/jats:italic>variants were identified in seven 46,<jats:styled-content style=\"fixed-case\">XY DSD<\/jats:styled-content>patients. These variants widely spread almost all the functional domains. Functional studies showed that novel mutations including p.S32N, p.N44del and p.G91D reduced transactivation of<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>11A1, while the other missense variant p.A168E did not impact protein function. All patients with<jats:italic><jats:styled-content style=\"fixed-case\">NR<\/jats:styled-content>5A1<\/jats:italic>rare variants had normal adrenal function and showed genital defects. Results of the genitalia examination showed female external genitalia (three patients), ambiguous external genitalia (two patients), female external genitalia with clitoromegaly (one patient), and hypospadias (one patient). All seven patients had bilateral testis and five of seven patients lacked M\u00fcllerian structures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Four novel mutations in the<jats:italic><jats:styled-content style=\"fixed-case\">NR<\/jats:styled-content>5A1<\/jats:italic>gene were identified in our cohort with 46,<jats:styled-content style=\"fixed-case\">XY DSD<\/jats:styled-content>, expanding the spectrum of<jats:italic><jats:styled-content style=\"fixed-case\">NR<\/jats:styled-content>5A1<\/jats:italic>gene mutations. All patients with<jats:italic><jats:styled-content style=\"fixed-case\">NR<\/jats:styled-content>5A1<\/jats:italic>rare variants had normal adrenal function and showed genital defects.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.13831","type":"journal-article","created":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T21:51:10Z","timestamp":1534197070000},"page":"613-620","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Novel<i><scp>NR<\/scp>5A1<\/i>mutations found in Chinese patients with 46,<scp>XY<\/scp>disorders of sex development"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0459-1923","authenticated-orcid":false,"given":"Bingqing","family":"Yu","sequence":"first","affiliation":[{"name":"NHC Key laboratory of Endocrinology Peking Union Medical College Hospital Beijing China"},{"name":"Department of Endocrinology Peking Union Medical College Hospital Peking Union 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