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Genotype–phenotype correlation, gonadal malignancy risk, gender preference, and testosterone/dihydrotestosterone ratio in steroid 5-alpha-reductase type 2 deficiency: a multicenter study from Turkey

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Abstract

Background

Studies regarding genetic and clinical characteristics, gender preference, and gonadal malignancy rates for steroid 5-alpha-reductase type 2 deficiency (5α-RD2) are limited and they were conducted on small number of patients.

Objective

To present genotype–phenotype correlation, gonadal malignancy risk, gender preference, and diagnostic sensitivity of serum testosterone/dihydrotestosterone (T/DHT) ratio in patients with 5α-RD2.

Materials and methods

Patients with variations in the SRD5A2 gene were included in the study. Demographic characteristics, phenotype, gender assignment, hormonal tests, molecular genetic data, and presence of gonadal malignancy were evaluated.

Results

A total of 85 patients were included in the study. Abnormality of the external genitalia was the most dominant phenotype (92.9%). Gender assignment was male in 58.8% and female in 29.4% of the patients, while it was uncertain for 11.8%. Fourteen patients underwent bilateral gonadectomy, and no gonadal malignancy was detected. The most frequent pathogenic variants were p.Ala65Pro (30.6%), p.Leu55Gln (16.5%), and p.Gly196Ser (15.3%). The p.Ala65Pro and p.Leu55Gln showed more undervirilization than the p.Gly196Ser. The diagnostic sensitivity of stimulated T/DHT ratio was higher than baseline serum T/DHT ratio, even in pubertal patients. The cut-off values yielding the best sensitivity for stimulated T/DHT ratio were ≥ 8.5 for minipuberty, ≥ 10 for prepuberty, and ≥ 17 for puberty.

Conclusion

There is no significant genotype–phenotype correlation in 5α-RD2. Gonadal malignancy risk seems to be low. If genetic analysis is not available at the time of diagnosis, stimulated T/DHT ratio can be useful, especially if different cut-off values are utilized in accordance with the pubertal status.

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References

  1. Wilson JD, Griffin JE, Russell DW (1993) Steroid 5 alpha-reductase 2 deficiency. Endocr Rev 14(5):577–593. https://doi.org/10.1210/edrv-14-5-577

    Article  CAS  PubMed  Google Scholar 

  2. Cheon CK (2011) Practical approach to steroid 5alpha-reductase type 2 deficiency. Eur J Pediatr 170(1):1–8. https://doi.org/10.1007/s00431-010-1189-4

    Article  CAS  PubMed  Google Scholar 

  3. Chan AO, But BW, Lee CY, Lam YY, Ng KL, Tung JY, Kwan EY, Chan YK, Tsui TK, Lam AL, Tse WY, Cheung PT, Shek CC (2013) Diagnosis of 5alpha-reductase 2 deficiency: is measurement of dihydrotestosterone essential? Clin Chem 59(5):798–806. https://doi.org/10.1373/clinchem.2012.196501

    Article  CAS  PubMed  Google Scholar 

  4. Maimoun L, Philibert P, Cammas B, Audran F, Bouchard P, Fenichel P, Cartigny M, Pienkowski C, Polak M, Skordis N, Mazen I, Ocal G, Berberoglu M, Reynaud R, Baumann C, Cabrol S, Simon D, Kayemba-Kay’s K, De Kerdanet M, Kurtz F, Leheup B, Heinrichs C, Tenoutasse S, Van Vliet G, Gruters A, Eunice M, Ammini AC, Hafez M, Hochberg Z, Einaudi S, Al Mawlawi H, Nunez CJ, Servant N, Lumbroso S, Paris F, Sultan C (2011) Phenotypical, biological, and molecular heterogeneity of 5alpha-reductase deficiency: an extensive international experience of 55 patients. J Clin Endocrinol Metab 96(2):296–307. https://doi.org/10.1210/jc.2010-1024

    Article  CAS  PubMed  Google Scholar 

  5. Cheng J, Lin R, Zhang W, Liu G, Sheng H, Li X, Zhou Z, Mao X, Liu L (2015) Phenotype and molecular characteristics in 45 Chinese children with 5alpha-reductase type 2 deficiency from South China. Clin Endocrinol (Oxf) 83(4):518–526. https://doi.org/10.1111/cen.12799

    Article  CAS  Google Scholar 

  6. Bertelloni S, Baldinotti F, Russo G, Ghirri P, Dati E, Michelucci A, Moscuzza F, Meroni S, Colombo I, Sessa MR, Baroncelli GI (2016) 5alpha-reductase-2 deficiency: clinical findings, endocrine pitfalls, and genetic features in a large Italian cohort. Sex Dev 10(1):28–36. https://doi.org/10.1159/000445090

    Article  CAS  PubMed  Google Scholar 

  7. Sinnecker GH, Hiort O, Dibbelt L, Albers N, Dorr HG, Hauss H, Heinrich U, Hemminghaus M, Hoepffner W, Holder M, Schnabel D, Kruse K (1996) Phenotypic classification of male pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency. Am J Med Genet 63(1):223–230. https://doi.org/10.1002/(SICI)1096-8628(19960503)63:1%3c223:AID-AJMG39%3e3.0.CO;2-O

    Article  CAS  PubMed  Google Scholar 

  8. Bertelloni S, Scaramuzzo RT, Parrini D, Baldinotti F, Tumini S, Ghirri P (2007) Early diagnosis of 5alpha-reductase deficiency in newborns. Sex Dev 1(3):147–151. https://doi.org/10.1159/000102103

    Article  CAS  PubMed  Google Scholar 

  9. Pang S, Levine LS, Chow D, Sagiani F, Saenger P, New MI (1979) Dihydrotestosterone and its relationship to testosterone in infancy and childhood. J Clin Endocrinol Metab 48(5):821–826. https://doi.org/10.1210/jcem-48-5-821

    Article  CAS  PubMed  Google Scholar 

  10. George MM, New MI, Ten S, Sultan C, Bhangoo A (2010) The clinical and molecular heterogeneity of 17betaHSD-3 enzyme deficiency. Horm Res Paediatr 74(4):229–240. https://doi.org/10.1159/000318004

    Article  CAS  PubMed  Google Scholar 

  11. Mendonca BB, Batista RL, Domenice S, Costa EM, Arnhold IJ, Russell DW, Wilson JD (2016) Steroid 5alpha-reductase 2 deficiency. J Steroid Biochem Mol Biol 163:206–211. https://doi.org/10.1016/j.jsbmb.2016.05.020

    Article  CAS  PubMed  Google Scholar 

  12. Adzhubei I, Jordan DM, Sunyaev SR (2013) Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet Chap 7(Unit7):20. https://doi.org/10.1002/0471142905.hg0720s76

    Article  Google Scholar 

  13. Pollard KS, Hubisz MJ, Rosenbloom KR, Siepel A (2010) Detection of nonneutral substitution rates on mammalian phylogenies. Genome Res 20(1):110–121. https://doi.org/10.1101/gr.097857.109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, Committee ALQA (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405–424. https://doi.org/10.1038/gim.2015.30

    Article  PubMed  PubMed Central  Google Scholar 

  15. Eren E, Edgunlu T, Asut E, Karakas Celik S (2016) Homozygous Ala65Pro mutation with V89L polymorphism in SRD5A2 deficiency. J Clin Res Pediatr Endocrinol 8(2):218–223. https://doi.org/10.4274/jcrpe.2495

    Article  PubMed  PubMed Central  Google Scholar 

  16. Akcay T, Fernandez-Cancio M, Turan S, Guran T, Audi L, Bereket A (2014) AR and SRD5A2 gene mutations in a series of 51 Turkish 46, XY DSD children with a clinical diagnosis of androgen insensitivity. Andrology 2(4):572–578. https://doi.org/10.1111/j.2047-2927.2014.00215.x

    Article  CAS  PubMed  Google Scholar 

  17. Boudon C, Lobaccaro JM, Lumbroso S, Ogur G, Ocal G, Belon C, Sultan C (1995) A new deletion of the 5 alpha-reductase type 2 gene in a Turkish family with 5 alpha-reductase deficiency. Clin Endocrinol (Oxf) 43(2):183–188

    Article  CAS  Google Scholar 

  18. Parlak M, Durmaz E, Gursoy S, Bircan I, Akcurin S (2014) Try235Phe homozygous mutation of the steroid 5-a reductase type 2 (SRD5A2) gene in a Turkish patient. Ann Saudi Med 34(3):254–256. https://doi.org/10.5144/0256-4947.2014.254

    Article  PubMed  PubMed Central  Google Scholar 

  19. Thigpen AE, Davis DL, Milatovich A, Mendonca BB, Imperato-McGinley J, Griffin JE, Francke U, Wilson JD, Russell DW (1992) Molecular genetics of steroid 5 alpha-reductase 2 deficiency. J Clin Invest 90(3):799–809. https://doi.org/10.1172/JCI115954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Vilchis F, Ramos L, Mendez JP, Benavides S, Canto P, Chavez B (2010) Molecular analysis of the SRD5A2 in 46, XY subjects with incomplete virilization: the P212R substitution of the steroid 5alpha-reductase 2 may constitute an ancestral founder mutation in Mexican patients. J Androl 31(4):358–364. https://doi.org/10.2164/jandrol.109.009407

    Article  CAS  PubMed  Google Scholar 

  21. Zhu H, Liu W, Han B, Fan M, Zhao S, Wang H, Lu Y, Pan C, Chen F, Chen M, Song H, Cheng K, Qiao J (2014) Phenotypic and molecular characteristics in eleven Chinese patients with 5alpha-reductase Type 2 deficiency. Clin Endocrinol (Oxf) 81(5):711–720. https://doi.org/10.1111/cen.12456

    Article  CAS  Google Scholar 

  22. Maimoun L, Philibert P, Bouchard P, Ocal G, Leheup B, Fenichel P, Servant N, Paris F, Sultan C (2011) Primary amenorrhea in four adolescents revealed 5alpha-reductase deficiency confirmed by molecular analysis. Fertil Steril 95(2):804. https://doi.org/10.1016/j.fertnstert.2010.08.007 (e801-805)

    Article  PubMed  Google Scholar 

  23. Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE (1974) Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science 186(4170):1213–1215

    Article  CAS  Google Scholar 

  24. Imperato-McGinley J, Miller M, Wilson JD, Peterson RE, Shackleton C, Gajdusek DC (1991) A cluster of male pseudohermaphrodites with 5 alpha-reductase deficiency in Papua New Guinea. Clin Endocrinol (Oxf) 34(4):293–298

    Article  CAS  Google Scholar 

  25. Adiyaman PB, Ocal G, Cetinkaya E, Akar N, Uysal A, Duman T, Evliyaoglu O, Aycan Z, Lumbroso S, Sultan C, Berberoglu M (2006) 5 alpha steroid reductase deficiency in Turkey. Pediatr Endocrinol Rev 3(Suppl 3):462–469

    PubMed  Google Scholar 

  26. Ocal G, Adiyaman P, Berberoglu M, Cetinkaya E, Akar N, Uysal A, Duman T, Evliyaoglu O, Aycan Z, Lumbroso S, Sultan C (2002) Mutations of the 5alpha-steroid reductase type 2 gene in six Turkish patients from unrelated families and a large pedigree of an isolated Turkish village. J Pediatr Endocrinol Metab 15(4):411–421

    Article  CAS  Google Scholar 

  27. Can S, Zhu YS, Cai LQ, Ling Q, Katz MD, Akgun S, Shackleton CH, Imperato-McGinley J (1998) The identification of 5 alpha-reductase-2 and 17 beta-hydroxysteroid dehydrogenase-3 gene defects in male pseudohermaphrodites from a Turkish kindred. J Clin Endocrinol Metab 83(2):560–569. https://doi.org/10.1210/jcem.83.2.4535

    Article  CAS  PubMed  Google Scholar 

  28. Savas Erdeve S, Aycan Z, Berberoglu M, Siklar Z, Hacihamdioglu B, Sipahi K, Akar N, Ocal G (2010) A novel mutation of 5alpha-steroid reductase 2 deficiency (CD 65 ALA-PRO) with severe virilization defect in a Turkish family and difficulty in gender assignment. Eur J Pediatr 169(8):991–995. https://doi.org/10.1007/s00431-010-1163-1

    Article  CAS  PubMed  Google Scholar 

  29. Canto P, Vilchis F, Chavez B, Mutchinick O, Imperato-McGinley J, Perez-Palacios G, Ulloa-Aguirre A, Mendez JP (1997) Mutations of the 5 alpha-reductase type 2 gene in eight Mexican patients from six different pedigrees with 5 alpha-reductase-2 deficiency. Clin Endocrinol (Oxf) 46(2):155–160

    Article  CAS  Google Scholar 

  30. Ferraz LF, Mathias Baptista MT, Maciel-Guerra AT, Junior GG, Hackel C (1999) New frameshift mutation in the 5alpha-reductase type 2 gene in a Brazilian patient with 5alpha-reductase deficiency. Am J Med Genet 87(3):221–225

    Article  CAS  Google Scholar 

  31. Hackel C, Oliveira LE, Ferraz LF, Tonini MM, Silva DN, Toralles MB, Stuchi-Perez EG, Guerra-Junior G (2005) New mutations, hotspots, and founder effects in Brazilian patients with steroid 5alpha-reductase deficiency type 2. J Mol Med (Berl) 83(7):569–576. https://doi.org/10.1007/s00109-005-0651-7

    Article  CAS  Google Scholar 

  32. Nie M, Zhou Q, Mao J, Lu S, Wu X (2011) Five novel mutations of SRD5A2 found in eight Chinese patients with 46, XY disorders of sex development. Mol Hum Reprod 17(1):57–62. https://doi.org/10.1093/molehr/gaq072

    Article  CAS  PubMed  Google Scholar 

  33. Sahu R, Boddula R, Sharma P, Bhatia V, Greaves R, Rao S, Desai M, Wakhlu A, Phadke S, Shukla M, Dabadghao P, Mehrotra RN, Bhatia E (2009) Genetic analysis of the SRD5A2 gene in Indian patients with 5alpha-reductase deficiency. J Pediatr Endocrinol Metab 22(3):247–254

    Article  CAS  Google Scholar 

  34. Mazen I, Hafez M, Mamdouh M, Sultan C, Lumbroso S (2003) A novel mutation of the 5alpha-reductase type 2 gene in two unrelated Egyptian children with ambiguous genitalia. J Pediatr Endocrinol Metab 16(2):219–224

    Article  CAS  Google Scholar 

  35. Hafez M, Mazen I, Ghali I, Sultan C, Lumbroso S (2003) A new mutation of 5-alpha-reductase type 2 (A62E) in a large Egyptian kindred. Horm Res 59(6):281–284

    CAS  PubMed  Google Scholar 

  36. Maimoun L, Philibert P, Cammas B, Audran F, Pienkowski C, Kurtz F, Heinrich C, Cartigny M, Sultan C (2010) Undervirilization in XY newborns may hide a 5alpha-reductase deficiency: report of three new SRD5A2 gene mutations. Int J Androl 33(6):841–847. https://doi.org/10.1111/j.1365-2605.2009.01036.x

    Article  CAS  PubMed  Google Scholar 

  37. Shabir I, Khurana ML, Joseph AA, Eunice M, Mehta M, Ammini AC (2015) Phenotype, genotype and gender identity in a large cohort of patients from India with 5alpha-reductase 2 deficiency. Andrology 3(6):1132–1139. https://doi.org/10.1111/andr.12108

    Article  CAS  PubMed  Google Scholar 

  38. Cohen-Kettenis PT (2005) Gender change in 46, XY persons with 5alpha-reductase-2 deficiency and 17beta-hydroxysteroid dehydrogenase-3 deficiency. Arch Sex Behav 34(4):399–410. https://doi.org/10.1007/s10508-005-4339-4

    Article  PubMed  Google Scholar 

  39. Wilson JD (2001) Androgens, androgen receptors, and male gender role behavior. Horm Behav 40(2):358–366. https://doi.org/10.1006/hbeh.2001.1684

    Article  CAS  PubMed  Google Scholar 

  40. Costa EM, Domenice S, Sircili MH, Inacio M, Mendonca BB (2012) DSD due to 5alpha-reductase 2 deficiency—from diagnosis to long term outcome. Semin Reprod Med 30(5):427–431. https://doi.org/10.1055/s-0032-1324727

    Article  CAS  PubMed  Google Scholar 

  41. Boudon C, Lumbroso S, Lobaccaro JM, Szarras-Czapnik M, Romer TE, Garandeau P, Montoya P, Sultan C (1995) Molecular study of the 5 alpha-reductase type 2 gene in three European families with 5 alpha-reductase deficiency. J Clin Endocrinol Metab 80(7):2149–2153. https://doi.org/10.1210/jcem.80.7.7608269

    Article  CAS  PubMed  Google Scholar 

  42. Mazen I, Gad YZ, Hafez M, Sultan C, Lumbroso S (2003) Molecular analysis of 5alpha-reductase type 2 gene in eight unrelated egyptian children with suspected 5alpha-reductase deficiency: prevalence of the G34R mutation. Clin Endocrinol (Oxf) 58(5):627–631

    Article  CAS  Google Scholar 

  43. Greaves RF, Jolly L, Hartmann MF, Ho CS, Kam RK, Joseph J, Boyder C, Wudy SA (2017) Harmonisation of serum dihydrotestosterone analysis: establishment of an external quality assurance program. Clin Chem Lab Med 55(4):522–529. https://doi.org/10.1515/cclm-2016-0394

    Article  CAS  PubMed  Google Scholar 

  44. Sasaki G, Ogata T, Ishii T, Kosaki K, Sato S, Homma K, Takahashi T, Hasegawa T, Matsuo N (2003) Micropenis and the 5alpha-reductase-2 (SRD5A2) gene: mutation and V89L polymorphism analysis in 81 Japanese patients. J Clin Endocrinol Metab 88(7):3431–3436. https://doi.org/10.1210/jc.2002-021415

    Article  CAS  PubMed  Google Scholar 

  45. Hughes IA, Houk C, Ahmed SF, Lee PA, Lawson Wilkins Pediatric Endocrine Society/European Society for Paediatric Endocrinology Consensus G (2006) Consensus statement on management of intersex disorders. J Pediatr Urol 2(3):148–162. https://doi.org/10.1016/j.jpurol.2006.03.004

    Article  CAS  PubMed  Google Scholar 

  46. Sasaki G, Nakagawa K, Hashiguchi A, Hasegawa T, Ogata T, Murai M (2003) Giant seminoma in a patient with 5 alpha-reductase type 2 deficiency. J Urol 169(3):1080–1081. https://doi.org/10.1097/01.ju.0000047621.66463.29

    Article  PubMed  Google Scholar 

  47. Vija L, Ferlicot S, Paun D, Bry-Gauillard H, Berdan G, Abd-Alsamad I, Lombes M, Young J (2014) Testicular histological and immunohistochemical aspects in a post-pubertal patient with 5 alpha-reductase type 2 deficiency: case report and review of the literature in a perspective of evaluation of potential fertility of these patients. BMC Endocr Disord 14:43. https://doi.org/10.1186/1472-6823-14-43

    Article  PubMed  PubMed Central  Google Scholar 

  48. Shaha C, Tripathi R, Mishra DP (2010) Male germ cell apoptosis: regulation and biology. Philos Trans R Soc Lond B Biol Sci 365(1546):1501–1515. https://doi.org/10.1098/rstb.2009.01

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to thank Feyza Darendeliler, Ömer Tarım, Aysun Bideci, Abdullah Bereket, Bilgin Yüksel, Murat Aydın, Yusuf Kenan Haspolat, Semra Çetinkaya, Teoman Akçay, and Ediz Yeşilkaya for their contributions to the study.

Funding

This work was supported financially by the Turkish Pediatric Endocrinology and Diabetes Society (Grant number: 032015).

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Authors and Affiliations

  1. Department of Pediatric Endocrinology, Faculty of Medicine, Dokuz Eylül University, Balcova, 35340, Izmir, Turkey

    A. Abacı

  2. Department of Pediatric Endocrinology, Faculty of Medicine, İzmir Katip Çelebi University, Izmir, Turkey

    G. Çatlı

  3. Division of Genetics, Tepecik Training and Research Hospital, Sağlık Bilimleri University, Izmir, Turkey

    Ö. Kırbıyık

  4. Department of Pediatric Endocrinology, Faculty of Medicine and Dr Sami Ulus Woman Health and Children Research Hospital, Yıldırım Beyazıt University, Ankara, Turkey

    N. M. Şahin & Z. Aycan

  5. Department of Pediatric Endocrinology, Faculty of Medicine, İstanbul University, İstanbul, Turkey

    Z. Y. Abalı & F. Baş

  6. Department of Pediatric Endocrinology, Faculty of Medicine, Dicle University, Diyarbakır, Turkey

    E. Ünal

  7. Department of Pediatric Endocrinology, Faculty of Medicine, Ankara University, Ankara, Turkey

    Z. Şıklar & M. Berberoğlu

  8. Department of Pediatric Endocrinology, Faculty of Medicine, Çukurova University, Adana, Turkey

    E. Mengen

  9. Department of Pediatric Endocrinology, Faculty of Medicine, Ege University, Izmir, Turkey

    S. Özen & Ş. Darcan

  10. Department of Pediatric Endocrinology, Faculty of Medicine, Marmara University, İstanbul, Turkey

    T. Güran

  11. Department of Pediatric Endocrinology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey

    C. Kara

  12. Division of Pediatric Endocrinology, Kanuni Sultan Süleyman Training and Research Hospital, İstanbul, Turkey

    M. Yıldız

  13. Department of Pediatric Endocrinology, Faculty of Medicine, Uludağ University, Bursa, Turkey

    E. Eren

  14. Division of Pediatric Endocrinology, Dr. Behcet Uz Children’s Hospital, Izmir, Turkey

    Ö. Nalbantoğlu

  15. Department of Pediatric Endocrinology, Göztepe Training and Research Hospital, İstanbul, Turkey

    A. Güven

  16. Department of Pediatric Endocrinology, Faculty of Medicine, Amasya University, Amasya, Turkey

    A. Güven

  17. Division of Pediatric Endocrinology, Erzurum Training and Research Hospital, Erzurum, Turkey

    A. Çayır

  18. Department of Pediatric Endocrinology, Faculty of Medicine, Gazi University, Ankara, Turkey

    E. D. Akbaş

  19. Department of Pediatric Endocrinology, Numune Training and Research Hospital, Sağlık Bilimleri University, Adana, Turkey

    Y. Kor

  20. Department of Pediatric Endocrinology, Sağlık Bilimleri University Antalya Training and Research Hospital, Antalya, Turkey

    Y. Çürek

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  1. A. Abacı
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Correspondence to A. Abacı.

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Abacı, A., Çatlı, G., Kırbıyık, Ö. et al. Genotype–phenotype correlation, gonadal malignancy risk, gender preference, and testosterone/dihydrotestosterone ratio in steroid 5-alpha-reductase type 2 deficiency: a multicenter study from Turkey. J Endocrinol Invest 42, 453–470 (2019). https://doi.org/10.1007/s40618-018-0940-y

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