{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:35:39Z","timestamp":1791477339101,"version":"4.3.4"},"reference-count":14,"publisher":"Endocrinology Research Centre","issue":"5","license":[{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.probl-endojournals.ru\/jour\/about\/editorialPolicies#openAccessPolicy"}],"content-domain":{"domain":["www.probl-endojournals.ru"],"crossmark-restriction":true},"short-container-title":["Probl Endokrinol (Mosk)"],"abstract":"<jats:p>Partial androgen resistance syndrome (PAIS) is the most difficult form of disorders\/differences of sex development 46,XY (DSD 46,XY) for choosing of patient management. To date, there are no clear biochemical criteria, especially before puberty, that allow differentiating PAIS from other PAIS-like forms of DSD 46, XY, and genetic verification of the partial form of AIS plays an important role. Meanwhile, according to the literature, mutations in the coding region of <jats:italic>AR<\/jats:italic> gene have not been identified in more than 50% of patients with suspected AIS. We performed an extensive analysis of the AR gene in a patient with clinical and laboratory signs of AIS and found a deep intron mutation in the <jats:italic>AR<\/jats:italic> gene (p. 2450\u201342G&gt;A). This variant creates an alternative splice acceptor site resulted a disturbance of the <jats:italic>AR<\/jats:italic> function. These findings indicate the need for extensive genetic analysis in a cohort of patients with suspected CPA in the absence of mutations in the <jats:italic>AR<\/jats:italic> gene using standard methods of genetic diagnosis.<\/jats:p>","DOI":"10.14341\/probl12799","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T07:31:07Z","timestamp":1636702267000},"page":"48-52","update-policy":"https:\/\/doi.org\/10.14341\/crossmarkpolicy2018","source":"Crossref","is-referenced-by-count":3,"title":["A deep intronic mutation in AR gene causing androgen insensitivity syndrome: difficulties of diagnostics"],"prefix":"10.14341","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2000-7694","authenticated-orcid":true,"given":"N. 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N.","family":"Tiulpakov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics; Republican children\u2019s clinical hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"5458","published-online":{"date-parts":[[2021,11,12]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Quigley CA, de Bellis A, Marschke KB, et al. Androgen Receptor Defects: Historical, Clinical, and Molecular Perspectives. Endocr Rev. 1995;16(3):271-321. doi: https:\/\/doi.org\/10.1210\/edrv-16-3-271","DOI":"10.1210\/edrv-16-3-271"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Lek N, Tadokoro-Cuccaro R, Whitchurch JB, et al. Predicting puberty in partial androgen insensitivity syndrome: Use of clinical and functional androgen receptor indices. EBioMedicine. 2018;36:401-409. doi: https:\/\/doi.org\/10.1016\/j.ebiom.2018.09.047","DOI":"10.1016\/j.ebiom.2018.09.047"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Lek N, Miles H, Bunch T, et al. Low frequency of androgen receptor gene mutations in 46 XY DSD, and fetal growth restriction. Arch Dis Child. 2014;99(4):358-361. doi: https:\/\/doi.org\/10.1136\/archdischild-2013-305338","DOI":"10.1136\/archdischild-2013-305338"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Lucas-Herald A, Bertelloni S, Juul A, et al. The Long-Term Outcome of Boys With Partial Androgen Insensitivity Syndrome and a Mutation in the Androgen Receptor Gene. J Clin Endocrinol Metab. 2016;101(11):3959-3967. doi: https:\/\/doi.org\/10.1210\/jc.2016-1372","DOI":"10.1210\/jc.2016-1372"},{"key":"ref5","unstructured":"Filatova AYu, Vasilyeva TA, Skoblov MYu, et al. Evidence of pathogenic role an intronic variant in PAX6 gene using functional analysis. Medical Genetics. 2018;17(4):42-46. (In Russ.). doi: https:\/\/doi.org\/10.25557\/2073-7998.2018.04.42-46"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Morris JM. The syndrome of testicular feminization in male pseudohermaphrodites. Am J Obstet Gynecol. 1953;65(6):1192-1211. doi: https:\/\/doi.org\/10.1016\/0002-9378(53)90359-7","DOI":"10.1016\/0002-9378(53)90359-7"},{"key":"ref7","unstructured":"Wilkins MDL. The Diagnosis and Treatment of Endocrine Disorders in Childhood and Adolescence. 1st Edition. Charles C. Thomas; 1950."},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Brown TR, Lubahn DB, Wilson EM, et al. Deletion of the steroid-binding domain of the human androgen receptor gene in one family with complete androgen insensitivity syndrome: evidence for further genetic heterogeneity in this syndrome. Proc Natl Acad Sci. 1988;85(21):8151-8155. doi: https:\/\/doi.org\/10.1073\/pnas.85.21.8151","DOI":"10.1073\/pnas.85.21.8151"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Lubahn DB, Brown TR, Simental JA, et al. Sequence of the intron\/exon junctions of the coding region of the human androgen receptor gene and identification of a point mutation in a family with complete androgen insensitivity. Proc Natl Acad Sci. 1989;86(23):9534-9538. doi: https:\/\/doi.org\/10.1073\/pnas.86.23.9534","DOI":"10.1073\/pnas.86.23.9534"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Parivesh A, Barseghyan H, D\u00e9lot E, Vilain E. Translating genomics to the clinical diagnosis of Disorders\/Differences of Sex Development. Curr Top Dev Biol. 2019;134:317-375. doi: https:\/\/doi.org\/10.1016\/bs.ctdb.2019.01.005","DOI":"10.1016\/bs.ctdb.2019.01.005"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Ris-Stalpers C, Kuiper GG, Faber PW, et al. Aberrant splicing of androgen receptor mRNA results in synthesis of a nonfunctional receptor protein in a patient with androgen insensitivity. Proc Natl Acad Sci U S A. 1990;87(20):7866-7870. doi: https:\/\/doi.org\/10.1073\/pnas.87.20.7866","DOI":"10.1073\/pnas.87.20.7866"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"K\u00e4ns\u00e4koski J, J\u00e4\u00e4skel\u00e4inen J, J\u00e4\u00e4skel\u00e4inen T, et al. Complete androgen insensitivity syndrome caused by a deep intronic pseudoexon-activating mutation in the androgen receptor gene. Sci Rep. 2016;6(1):32819. doi: https:\/\/doi.org\/10.1038\/srep32819","DOI":"10.1038\/srep32819"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Br\u00fcggenwirth HT, Boehmer ALM, Ramnarain S, et al. Molecular Analysis of the Androgen-Receptor Gene in a Family with Receptor-Positive Partial Androgen Insensitivity: An Unusual Type of Intronic Mutation. Am J Hum Genet. 1997;61(5):1067-1077. doi: https:\/\/doi.org\/10.1086\/301605","DOI":"10.1086\/301605"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Ono H, Saitsu H, Horikawa R, et al. Partial androgen insensitivity syndrome caused by a deep intronic mutation creating an alternative splice acceptor site of the AR gene. 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