{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:29:47Z","timestamp":1773289787371,"version":"3.50.1"},"reference-count":20,"publisher":"The Endocrine Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,9,1]]},"abstract":"<jats:p>Context: The SRY gene encodes a transcription factor responsible for initiating testis differentiation. Mutations in SRY almost always result in XY sex reversal with pure gonadal dysgenesis and an increased risk of gonadal tumor. Most of these mutations are de novo, affecting only one individual in a family. Only a small subset of mutations is shared between a phenotypically normal father and one or more of his affected children. Incomplete penetrance and somatic mosaicism are two hypotheses that may explain a normal phenotype in a father carrying a SRY mutation.<\/jats:p>\n               <jats:p>Patients and Results: We describe a family with two sisters with XY sex reversal and pure gonadal dysgenesis and a phenotypically normal brother. A novel constitutional frameshift SRY mutation was identified in both sisters and was absent in the brother. The single base pair deletion (c.71delA) led to a premature stop codon in position 60 of the protein, removing entirely the high-mobility group domain and the DNA-binding domain of SRY. The father of the three children presented with hypospadias; cryptorchidism; testicular seminoma and oligoasthenozoospermia, an association termed testicular dysgenesis syndrome (TDS); and the SRY mutation in a mosaic state in the peripheral blood and the tumor.<\/jats:p>\n               <jats:p>Conclusions: This observation of somatic and germinal mosaicism for a SRY mutation may explain the variable penetrance in some familial gonadal dysgenesis. Importantly, the present report is the first one describing the association of SRY mutation in a male with TDS. This suggests that mutations in a sex-determining gene may contribute to the pathogenesis of TDS.<\/jats:p>\n               <jats:p>A fertile man is described with hypospadias, cryptorchidism, testicular seminoma, and oligoasthenozoospermia, and a mosaic SRY mutation.<\/jats:p>","DOI":"10.1210\/jc.2009-0226","type":"journal-article","created":{"date-parts":[[2009,6,17]],"date-time":"2009-06-17T00:54:28Z","timestamp":1245200068000},"page":"3467-3471","source":"Crossref","is-referenced-by-count":36,"title":["Familial Frameshift SRY Mutation Inherited from a Mosaic Father with Testicular Dysgenesis Syndrome"],"prefix":"10.1210","volume":"94","author":[{"given":"Bertrand","family":"Isidor","sequence":"first","affiliation":[{"name":"CHU Nantes, Service de Ge\u0301ne\u0301tique Me\u0301dicale (B.I., M.G., A.D., C.L.C.), 44000 Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Capito","sequence":"additional","affiliation":[{"name":"Service de Chirurgie Infantile (C.C., M.-D.L.), 44000 Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franc\u0327oise","family":"Paris","sequence":"additional","affiliation":[{"name":"Service d\u2019Hormonologie (F.P., C.S.), Ho\u0302pital Lapeyronie, CHU Montpellier, F-34295 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Baron","sequence":"additional","affiliation":[{"name":"Clinique Me\u0301diale Pe\u0301diatrique (S.B.), 44000 Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nade\u0300ge","family":"Corradini","sequence":"additional","affiliation":[{"name":"Service d\u2019Oncologie Pe\u0301diatrique (N.C., B.C.), 44000 Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blandine","family":"Cabaret","sequence":"additional","affiliation":[{"name":"Service d\u2019Oncologie Pe\u0301diatrique (N.C., B.C.), 44000 Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc-David","family":"Leclair","sequence":"additional","affiliation":[{"name":"Service de Chirurgie Infantile (C.C., M.-D.L.), 44000 Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathilde","family":"Giraud","sequence":"additional","affiliation":[{"name":"CHU Nantes, Service de Ge\u0301ne\u0301tique Me\u0301dicale (B.I., M.G., A.D., C.L.C.), 44000 Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Martin-Coignard","sequence":"additional","affiliation":[{"name":"Unite\u0301 de Ge\u0301ne\u0301tique Clinique (D.M.-C.), Centre Hospitalier du Mans, 72000 Le Mans, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"David","sequence":"additional","affiliation":[{"name":"CHU Nantes, Service de Ge\u0301ne\u0301tique Me\u0301dicale (B.I., M.G., A.D., C.L.C.), 44000 Nantes, 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motif.","volume":"346","author":"Sinclair","year":"1990","journal-title":"Nature"},{"key":"2020071613360785600_R2","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/humu.10212","article-title":"Human Gene Mutation Database (HGMD): 2003 update.","volume":"21","author":"Stenson","year":"2003","journal-title":"Hum Mutat"},{"key":"2020071613360785600_R3","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/BF02267082","article-title":"novel postzygotic nonsense mutation in SRY in familial XY gonadal dysgenesis.","volume":"97","author":"Bilbao","year":"1996","journal-title":"Hum Genet"},{"key":"2020071613360785600_R4","first-page":"862","article-title":"Two novel SRY missense mutations reducing DNA binding identified in XY females and their mosaic fathers.","volume":"56","author":"Schmitt-Ney","year":"1995","journal-title":"Am J Hum 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case.","volume":"52","author":"Braun","year":"1993","journal-title":"Am J Hum Genet"},{"key":"2020071613360785600_R17","first-page":"701","article-title":"Analysis of the SRY gene in gonadal tissue of subjects with 46,XY gonadal dysgenesis.","volume":"82","author":"Fuqua","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613360785600_R18","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/sj.ejhg.5201232","article-title":"Mutation analysis of five candidate genes in Chinese patients with hypospadias.","volume":"12","author":"Wang","year":"2004","journal-title":"Eur J Hum Genet"},{"key":"2020071613360785600_R19","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1289\/ehp.99107297","article-title":"International trends in rates of hypospadias and cryptorchidism.","volume":"107","author":"Paulozzi","year":"1999","journal-title":"Environ Health 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