A novel, homozygous mutation in desert hedgehog (DHH) in a 46, XY patient with dysgenetic testes presenting with primary amenorrhoea: a case report

go back to reference Mendonca BB, Domenice S, Arnhold IJ, Costa EM. 46, XY disorders of sex development (DSD). Clin Endocrinol. 2009;70:173–87. Mendonca BB, Domenice S, Arnhold IJ, Costa EM. 46, XY disorders of sex development (DSD). Clin Endocrinol. 2009;70:173–87.

go back to reference Arboleda VA, Sandberg DE, Vilain E. DSDs: genetics, underlying pathologies and psychosexual differentiation. Nat Rev Endocrinol. 2014;10:603–15.CrossRefPubMedPubMedCentral Arboleda VA, Sandberg DE, Vilain E. DSDs: genetics, underlying pathologies and psychosexual differentiation. Nat Rev Endocrinol. 2014;10:603–15.CrossRefPubMedPubMedCentral

go back to reference Rey R, Josso N, Racine C. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Sexual Differentiation. South Dartmouth (MA): Endotext; 2000. Rey R, Josso N, Racine C. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Sexual Differentiation. South Dartmouth (MA): Endotext; 2000.

go back to reference Ocal G. Current concepts in disorders of sexual development. J Clin Res Pediatr Endocrinol. 2011;3:105–14.CrossRefPubMedPubMedCentral Ocal G. Current concepts in disorders of sexual development. J Clin Res Pediatr Endocrinol. 2011;3:105–14.CrossRefPubMedPubMedCentral

go back to reference Clark AM, Garland KK, Russell LD. Desert hedgehog (Dhh) gene is required in the mouse testis for formation of adult-type Leydig cells and normal development of peritubular cells and seminiferous tubules. Biol Reprod. 2000;63:1825–38.CrossRefPubMed Clark AM, Garland KK, Russell LD. Desert hedgehog (Dhh) gene is required in the mouse testis for formation of adult-type Leydig cells and normal development of peritubular cells and seminiferous tubules. Biol Reprod. 2000;63:1825–38.CrossRefPubMed

go back to reference Ahmed SF, Achermann JC, Arlt W, Balen A, Conway G, Edwards Z, Elford S, Hughes IA, Izatt L, Krone N, Miles H, O'Toole S, Perry L, Sanders C, Simmonds M, Watt A, Willis D. Society for Endocrinology UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development (revised 2015). Clin Endocrinol. 2016;84:771–88.CrossRef Ahmed SF, Achermann JC, Arlt W, Balen A, Conway G, Edwards Z, Elford S, Hughes IA, Izatt L, Krone N, Miles H, O'Toole S, Perry L, Sanders C, Simmonds M, Watt A, Willis D. Society for Endocrinology UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development (revised 2015). Clin Endocrinol. 2016;84:771–88.CrossRef

go back to reference Juniarto AZ, van der Zwan YG, Santosa A, Ariani MD, Eggers S, Hersmus R, Themmen AP, Bruggenwirth HT, Wolffenbuttel KP, Sinclair A, White SJ, Looijenga LH, de Jong FH, Faradz SM, Drop SL. Hormonal evaluation in relation to phenotype and genotype in 286 patients with a disorder of sex development from Indonesia. Clin Endocrinol. 2016;85:247–57.CrossRef Juniarto AZ, van der Zwan YG, Santosa A, Ariani MD, Eggers S, Hersmus R, Themmen AP, Bruggenwirth HT, Wolffenbuttel KP, Sinclair A, White SJ, Looijenga LH, de Jong FH, Faradz SM, Drop SL. Hormonal evaluation in relation to phenotype and genotype in 286 patients with a disorder of sex development from Indonesia. Clin Endocrinol. 2016;85:247–57.CrossRef

go back to reference Wu JY, McGown IN, Lin L, Achermann JC, Harris M, Cowley DM, Aftimos S, Neville KA, Choong CS, Cotterill AM. A novel NR5A1 variant in an infant with elevated testosterone from an Australasian cohort of 46, XY patients with disorders of sex development. Clin Endocrinol. 2013;78:545–50.CrossRef Wu JY, McGown IN, Lin L, Achermann JC, Harris M, Cowley DM, Aftimos S, Neville KA, Choong CS, Cotterill AM. A novel NR5A1 variant in an infant with elevated testosterone from an Australasian cohort of 46, XY patients with disorders of sex development. Clin Endocrinol. 2013;78:545–50.CrossRef

go back to reference Achermann JC, Domenice S, Bachega TA, Nishi MY, Mendonca BB. Disorders of sex development: effect of molecular diagnostics. Nat Rev Endocrinol. 2015;11:478–88.CrossRefPubMed Achermann JC, Domenice S, Bachega TA, Nishi MY, Mendonca BB. Disorders of sex development: effect of molecular diagnostics. Nat Rev Endocrinol. 2015;11:478–88.CrossRefPubMed

go back to reference Eggers S, Sadedin S, van den Bergen JA, Robevska G, Ohnesorg T, Hewitt J, Lambeth L, Bouty A, Knarston IM, Tan TY, Cameron F, Werther G, Hutson J, O'Connell M, Grover SR, Heloury Y, Zacharin M, Bergman P, Kimber C, Brown J, Webb N, Hunter MF, Srinivasan S, Titmuss A, Verge CF, Mowat D, Smith G, Smith J, Ewans L, Shalhoub C, Crock P, Cowell C, Leong GM, Ono M, Lafferty AR, Huynh T, Visser U, Choong CS, McKenzie F, Pachter N, Thompson EM, Couper J, Baxendale A, Gecz J, Wheeler BJ, Jefferies C, MacKenzie K, Hofman P, Carter P, King RI, Krausz C, van Ravenswaaij-Arts CM, Looijenga L, Drop S, Riedl S, Cools M, Dawson A, Juniarto AZ, Khadilkar V, Khadilkar A, Bhatia V, Dung VC, Atta I, Raza J, Thi Diem Chi N, Hao TK, Harley V, Koopman P, Warne G, Faradz S, Oshlack A, Ayers KL, Sinclair AH. Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort. Genome Biol. 2016;17:243.CrossRefPubMedPubMedCentral Eggers S, Sadedin S, van den Bergen JA, Robevska G, Ohnesorg T, Hewitt J, Lambeth L, Bouty A, Knarston IM, Tan TY, Cameron F, Werther G, Hutson J, O'Connell M, Grover SR, Heloury Y, Zacharin M, Bergman P, Kimber C, Brown J, Webb N, Hunter MF, Srinivasan S, Titmuss A, Verge CF, Mowat D, Smith G, Smith J, Ewans L, Shalhoub C, Crock P, Cowell C, Leong GM, Ono M, Lafferty AR, Huynh T, Visser U, Choong CS, McKenzie F, Pachter N, Thompson EM, Couper J, Baxendale A, Gecz J, Wheeler BJ, Jefferies C, MacKenzie K, Hofman P, Carter P, King RI, Krausz C, van Ravenswaaij-Arts CM, Looijenga L, Drop S, Riedl S, Cools M, Dawson A, Juniarto AZ, Khadilkar V, Khadilkar A, Bhatia V, Dung VC, Atta I, Raza J, Thi Diem Chi N, Hao TK, Harley V, Koopman P, Warne G, Faradz S, Oshlack A, Ayers KL, Sinclair AH. Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort. Genome Biol. 2016;17:243.CrossRefPubMedPubMedCentral

go back to reference Umehara F, Tate G, Itoh K, Yamaguchi N, Douchi T, Mitsuya T, Osame M. A novel mutation of desert hedgehog in a patient with 46,XY partial gonadal dysgenesis accompanied by minifascicular neuropathy. Am J Hum Genet. 2000;67:1302–5.CrossRefPubMedPubMedCentral Umehara F, Tate G, Itoh K, Yamaguchi N, Douchi T, Mitsuya T, Osame M. A novel mutation of desert hedgehog in a patient with 46,XY partial gonadal dysgenesis accompanied by minifascicular neuropathy. Am J Hum Genet. 2000;67:1302–5.CrossRefPubMedPubMedCentral

go back to reference Canto P, Soderlund D, Reyes E, Mendez JP. Mutations in the desert hedgehog (DHH) gene in patients with 46, XY complete pure gonadal dysgenesis. J Clin Endocrinol Metab. 2004;89:4480–3.CrossRefPubMed Canto P, Soderlund D, Reyes E, Mendez JP. Mutations in the desert hedgehog (DHH) gene in patients with 46, XY complete pure gonadal dysgenesis. J Clin Endocrinol Metab. 2004;89:4480–3.CrossRefPubMed

go back to reference Das DK, Sanghavi D, Gawde H, Idicula-Thomas S, Vasudevan L. Novel homozygous mutations in desert hedgehog gene in patients with 46, XY complete gonadal dysgenesis and prediction of its structural and functional implications by computational methods. Eur J Med Genet. 2011;54:e529–34.CrossRefPubMed Das DK, Sanghavi D, Gawde H, Idicula-Thomas S, Vasudevan L. Novel homozygous mutations in desert hedgehog gene in patients with 46, XY complete gonadal dysgenesis and prediction of its structural and functional implications by computational methods. Eur J Med Genet. 2011;54:e529–34.CrossRefPubMed

go back to reference Werner R, Merz H, Birnbaum W, Marshall L, Schroder T, Reiz B, Kavran JM, Baumer T, Capetian P, Hiort O. 46, XY gonadal Dysgenesis due to a homozygous mutation in desert hedgehog (DHH) identified by exome sequencing. J Clin Endocrinol Metab. 2015;100:E1022–9.CrossRefPubMedPubMedCentral Werner R, Merz H, Birnbaum W, Marshall L, Schroder T, Reiz B, Kavran JM, Baumer T, Capetian P, Hiort O. 46, XY gonadal Dysgenesis due to a homozygous mutation in desert hedgehog (DHH) identified by exome sequencing. J Clin Endocrinol Metab. 2015;100:E1022–9.CrossRefPubMedPubMedCentral

go back to reference Sato NS, Maekawa R, Ishiura H, Mitsui J, Naruse H, Tokushige SI, Sugie K, Tate G, Shimizu J, Goto J, Tsuji S, Shiio Y. Partial duplication of DHH causes minifascicular neuropathy: a novel mutation detection of DHH. Ann Clin Transl Neurol. 2017;4:415–21.CrossRefPubMedPubMedCentral Sato NS, Maekawa R, Ishiura H, Mitsui J, Naruse H, Tokushige SI, Sugie K, Tate G, Shimizu J, Goto J, Tsuji S, Shiio Y. Partial duplication of DHH causes minifascicular neuropathy: a novel mutation detection of DHH. Ann Clin Transl Neurol. 2017;4:415–21.CrossRefPubMedPubMedCentral

go back to reference Sugie K, Futamura N, Suzumura A, Tate G, Umehara F. Hereditary motor and sensory neuropathy with minifascicle formation in a patient with 46, XY pure gonadal dysgenesis: a new clinical entity. Ann Neurol. 2002;51:385–8.CrossRefPubMed Sugie K, Futamura N, Suzumura A, Tate G, Umehara F. Hereditary motor and sensory neuropathy with minifascicle formation in a patient with 46, XY pure gonadal dysgenesis: a new clinical entity. Ann Neurol. 2002;51:385–8.CrossRefPubMed

go back to reference Paris F, Flatters D, Caburet S, Legois B, Servant N, Lefebvre H, Sultan C, Veitia RA. A novel variant of DHH in a familial case of 46, XY disorder of sex development: insights from molecular dynamics simulations. Clin Endocrinol. 2017;87:539–44.CrossRef Paris F, Flatters D, Caburet S, Legois B, Servant N, Lefebvre H, Sultan C, Veitia RA. A novel variant of DHH in a familial case of 46, XY disorder of sex development: insights from molecular dynamics simulations. Clin Endocrinol. 2017;87:539–44.CrossRef

go back to reference Callens N, Van Kuyk M, van Kuppenveld JH, Drop SL, Cohen-Kettenis PT, Dessens AB. Dutch study group on DSD. Recalled and current gender role behavior, gender identity and sexual orientation in adults with disorders/differences of sex development. Horm Behav. 2016;86:8–20.CrossRefPubMed Callens N, Van Kuyk M, van Kuppenveld JH, Drop SL, Cohen-Kettenis PT, Dessens AB. Dutch study group on DSD. Recalled and current gender role behavior, gender identity and sexual orientation in adults with disorders/differences of sex development. Horm Behav. 2016;86:8–20.CrossRefPubMed

go back to reference Cohen-Kettenis PT. Gender change in 46, XY persons with 5alpha-reductase-2 deficiency and 17beta-hydroxysteroid dehydrogenase-3 deficiency. Arch Sex Behav. 2005;34:399–410.CrossRefPubMed Cohen-Kettenis PT. Gender change in 46, XY persons with 5alpha-reductase-2 deficiency and 17beta-hydroxysteroid dehydrogenase-3 deficiency. Arch Sex Behav. 2005;34:399–410.CrossRefPubMed

go back to reference Furtado PS, Moraes F, Lago R, Barros LO, Toralles MB, Barroso U Jr. Gender dysphoria associated with disorders of sex development. Nat Rev Urol. 2012;9:620–7.CrossRefPubMed Furtado PS, Moraes F, Lago R, Barros LO, Toralles MB, Barroso U Jr. Gender dysphoria associated with disorders of sex development. Nat Rev Urol. 2012;9:620–7.CrossRefPubMed

go back to reference Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7:248–9.CrossRefPubMedPubMedCentral Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7:248–9.CrossRefPubMedPubMedCentral

go back to reference Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009;4:1073–81.CrossRefPubMed Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009;4:1073–81.CrossRefPubMed

go back to reference Shihab HA, Gough J, Cooper DN, Stenson PD, Barker GL, Edwards KJ, Day IN, Gaunt TR. Predicting the functional, molecular, and phenotypic consequences of amino acid substitutions using hidden Markov models. Hum Mutat. 2013;34:57–65.CrossRefPubMed Shihab HA, Gough J, Cooper DN, Stenson PD, Barker GL, Edwards KJ, Day IN, Gaunt TR. Predicting the functional, molecular, and phenotypic consequences of amino acid substitutions using hidden Markov models. Hum Mutat. 2013;34:57–65.CrossRefPubMed

go back to reference Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O'Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB, Tukiainen T, Birnbaum DP, Kosmicki JA, Duncan LE, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper DN, Deflaux N, DePristo M, Do R, Flannick J, Fromer M, Gauthier L, Goldstein J, Gupta N, Howrigan D, Kiezun A, Kurki MI, Moonshine AL, Natarajan P, Orozco L, Peloso GM, Poplin R, Rivas MA, Ruano-Rubio V, Rose SA, Ruderfer DM, Shakir K, Stenson PD, Stevens C, Thomas BP, Tiao G, Tusie-Luna MT, Weisburd B, Won HH, Yu D, Altshuler DM, Ardissino D, Boehnke M, Danesh J, Donnelly S, Elosua R, Florez JC, Gabriel SB, Getz G, Glatt SJ, Hultman CM, Kathiresan S, Laakso M, McCarroll S, McCarthy MI, McGovern D, McPherson R, Neale BM, Palotie A, Purcell SM, Saleheen D, Scharf JM, Sklar P, Sullivan PF, Tuomilehto J, Tsuang MT, Watkins HC, Wilson JG, Daly MJ, MacArthur DG, Exome Aggregation C. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536:285–91.CrossRefPubMedPubMedCentral Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O'Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB, Tukiainen T, Birnbaum DP, Kosmicki JA, Duncan LE, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper DN, Deflaux N, DePristo M, Do R, Flannick J, Fromer M, Gauthier L, Goldstein J, Gupta N, Howrigan D, Kiezun A, Kurki MI, Moonshine AL, Natarajan P, Orozco L, Peloso GM, Poplin R, Rivas MA, Ruano-Rubio V, Rose SA, Ruderfer DM, Shakir K, Stenson PD, Stevens C, Thomas BP, Tiao G, Tusie-Luna MT, Weisburd B, Won HH, Yu D, Altshuler DM, Ardissino D, Boehnke M, Danesh J, Donnelly S, Elosua R, Florez JC, Gabriel SB, Getz G, Glatt SJ, Hultman CM, Kathiresan S, Laakso M, McCarroll S, McCarthy MI, McGovern D, McPherson R, Neale BM, Palotie A, Purcell SM, Saleheen D, Scharf JM, Sklar P, Sullivan PF, Tuomilehto J, Tsuang MT, Watkins HC, Wilson JG, Daly MJ, MacArthur DG, Exome Aggregation C. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536:285–91.CrossRefPubMedPubMedCentral

go back to reference Genomes Project C, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, Abecasis GR. A Global reference for human genetic variation. Nature. 2015;526:68–74.CrossRef Genomes Project C, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, Abecasis GR. A Global reference for human genetic variation. Nature. 2015;526:68–74.CrossRef

go back to reference Tennessen JA, Bigham AW, O'Connor TD, Fu W, Kenny EE, Gravel S, McGee S, Do R, Liu X, Jun G, Kang HM, Jordan D, Leal SM, Gabriel S, Rieder MJ, Abecasis G, Altshuler D, Nickerson DA, Boerwinkle E, Sunyaev S, Bustamante CD, Bamshad MJ, Akey JM, Broad GO, Seattle GO, Project NES. Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science. 2012;337:64–9.CrossRefPubMedPubMedCentral Tennessen JA, Bigham AW, O'Connor TD, Fu W, Kenny EE, Gravel S, McGee S, Do R, Liu X, Jun G, Kang HM, Jordan D, Leal SM, Gabriel S, Rieder MJ, Abecasis G, Altshuler D, Nickerson DA, Boerwinkle E, Sunyaev S, Bustamante CD, Bamshad MJ, Akey JM, Broad GO, Seattle GO, Project NES. Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science. 2012;337:64–9.CrossRefPubMedPubMedCentral

go back to reference Biasini M, Bienert S, Waterhouse A, Arnold K, Studer G, Schmidt T, Kiefer F, Gallo Cassarino T, Bertoni M, Bordoli L, Schwede T. SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res. 2014;42:W252–8.CrossRefPubMedPubMedCentral Biasini M, Bienert S, Waterhouse A, Arnold K, Studer G, Schmidt T, Kiefer F, Gallo Cassarino T, Bertoni M, Bordoli L, Schwede T. SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res. 2014;42:W252–8.CrossRefPubMedPubMedCentral

go back to reference Venselaar H, Te Beek TA, Kuipers RK, Hekkelman ML, Vriend G. Protein structure analysis of mutations causing inheritable diseases. An e-science approach with life scientist friendly interfaces. BMC Bioinformatics. 2010;11:548.CrossRefPubMedPubMedCentral Venselaar H, Te Beek TA, Kuipers RK, Hekkelman ML, Vriend G. Protein structure analysis of mutations causing inheritable diseases. An e-science approach with life scientist friendly interfaces. BMC Bioinformatics. 2010;11:548.CrossRefPubMedPubMedCentral

go back to reference Hughes IA, Houk C, Ahmed SF, Lee PA. Lawson Wilkins pediatric Endocrine Society/European Society for Paediatric Endocrinology Consensus Group. Consensus statement on management of intersex disorders. J Pediatr Urol. 2006;2:148–62.CrossRefPubMed Hughes IA, Houk C, Ahmed SF, Lee PA. Lawson Wilkins pediatric Endocrine Society/European Society for Paediatric Endocrinology Consensus Group. Consensus statement on management of intersex disorders. J Pediatr Urol. 2006;2:148–62.CrossRefPubMed

go back to reference Hiort O, Birnbaum W, Marshall L, Wunsch L, Werner R, Schroder T, Dohnert U, Holterhus PM. Management of disorders of sex development. Nat Rev Endocrinol. 2014;10:520–9.CrossRefPubMed Hiort O, Birnbaum W, Marshall L, Wunsch L, Werner R, Schroder T, Dohnert U, Holterhus PM. Management of disorders of sex development. Nat Rev Endocrinol. 2014;10:520–9.CrossRefPubMed

go back to reference Bitgood MJ, Shen L, McMahon AP. Sertoli cell signaling by desert hedgehog regulates the male germline. Curr Biol. 1996;6:298–304.CrossRefPubMed Bitgood MJ, Shen L, McMahon AP. Sertoli cell signaling by desert hedgehog regulates the male germline. Curr Biol. 1996;6:298–304.CrossRefPubMed

go back to reference Parmantier E, Lynn B, Lawson D, Turmaine M, Namini SS, Chakrabarti L, McMahon AP, Jessen KR, Mirsky R. Schwann cell-derived desert hedgehog controls the development of peripheral nerve sheaths. Neuron. 1999;23:713–24.CrossRefPubMed Parmantier E, Lynn B, Lawson D, Turmaine M, Namini SS, Chakrabarti L, McMahon AP, Jessen KR, Mirsky R. Schwann cell-derived desert hedgehog controls the development of peripheral nerve sheaths. Neuron. 1999;23:713–24.CrossRefPubMed

go back to reference Bitgood MJ, McMahon AP. Hedgehog and bmp genes are coexpressed at many diverse sites of cell-cell interaction in the mouse embryo. Dev Biol. 1995;172:126–38.CrossRefPubMed Bitgood MJ, McMahon AP. Hedgehog and bmp genes are coexpressed at many diverse sites of cell-cell interaction in the mouse embryo. Dev Biol. 1995;172:126–38.CrossRefPubMed

go back to reference Umehara F, Yamaguchi N, Kodama D, Takenaga S, Kiwaki T, Sonoda Y, Arimura Y, Yamada H, Arimura K, Osame M. Polyneuropathy with minifascicle formation in a patient with 46, XY mixed gonadal dysgenesis. Acta Neuropathol. 1999;98:309–12.CrossRefPubMed Umehara F, Yamaguchi N, Kodama D, Takenaga S, Kiwaki T, Sonoda Y, Arimura Y, Yamada H, Arimura K, Osame M. Polyneuropathy with minifascicle formation in a patient with 46, XY mixed gonadal dysgenesis. Acta Neuropathol. 1999;98:309–12.CrossRefPubMed

go back to reference Canto P, Vilchis F, Soderlund D, Reyes E, Mendez JP. A heterozygous mutation in the desert hedgehog gene in patients with mixed gonadal dysgenesis. Mol Hum Reprod. 2005;11:833–6.CrossRefPubMed Canto P, Vilchis F, Soderlund D, Reyes E, Mendez JP. A heterozygous mutation in the desert hedgehog gene in patients with mixed gonadal dysgenesis. Mol Hum Reprod. 2005;11:833–6.CrossRefPubMed

go back to reference Jurgensen M, Kleinemeier E, Lux A, Steensma TD, Cohen-Kettenis PT, Hiort O, Thyen U, Kohler B. Psychosexual development in adolescents and adults with disorders of sex development--results from the German clinical evaluation study. J Sex Med. 2013;10:2703–14.CrossRefPubMed Jurgensen M, Kleinemeier E, Lux A, Steensma TD, Cohen-Kettenis PT, Hiort O, Thyen U, Kohler B. Psychosexual development in adolescents and adults with disorders of sex development--results from the German clinical evaluation study. J Sex Med. 2013;10:2703–14.CrossRefPubMed