A Novel p.Arg179Ser (c.537 G>T) Heterozygotes Mutation on Exon 3 Of SRD5A2 Gene Accompany With Biotidinase Deficiency In Case With Ambiguous External Genitalia

Year 2017, Volume: 9 Issue: 3, 278 - 282, 22.09.2017

Semih Bolu , Recep Eroz , Mustafa Dogan , Ilknur Arslanoglu , Emrah Gun Huseyin Yuce

https://doi.org/10.18521/ktd.341688

https://izlik.org/JA26LK93WM

Abstract

The SRD5A2 gene that
encodes SRD5A2 enzyme is placed on
chromosome 2p23. The coding region of the gene includes 5 exons that are
translated into a 254-amino acid protein. To evaluate
SRD5A2 gene that encodes SRD5A2
enzyme is placed on chromosome 2p23 accompany
with biotidinase deficiency in case with ambiguous external genitalia. We investigated a case with ambiguous external genitalia for cytogenetic and gene mutation
analaysis. Gene mutation analaysis and cytogenetic analaysis were performed
according to a standard DNA
sequencing method based on PCR and the present
international standard nomenclature (ISCN), respectively. A Novel p.Arg179Ser (c.537 G>T) heterozygotes mutation
on exon 3 of SRD5A2 gene accompany
with biotidinase deficiency was detected. The chromosomal analaysis result is
46, XY. This is the
first case with biotinidase deficiency and novel R179S p.Arg179Ser (c.537 G>T) mutation of the SRD5A2
gene, which cause 5-alpha reductase deficiency.

Keywords

SRD5A2 , Ambiguous External Genitalia

References

• References 1. Parisi MA, Ramsdell LA, Burns MW, Carr MC, Grady RE, Gunther DF, Kletter GB, McCauley E, Mitchell ME, Opheim KE, Pihoker C, Richards GE, Soules MR, Pagon RA. A Gender Assessment Team: experience with 250 patients over a period of 25 years. Genet Medicine 2007;9:348-357. 2. Maimoun L, Philibert P, Cammas B, Audran F, Pienkowski C, Kurtz F, Heinrich C, Cartigny M, Sultan C. Undervirilization in XY newborns may hide a 5α-reductase deficiency: report of three new SRD5A2 gene mutations. International Journal of Andrology 2010;33:841-847. (doi: 10.1111/j.1365-2605.2009.01036.x.) 3. Berra M, Williams EL, Muroni B, Creighton SM, Honour JW, Rumsby G, Conway GS. Recognition of 5α-reductase-2 deficiency in an adult female 46XY DSD clinic. European Journal of Endocrinology 2011;164:1019-1025. (doi: 10.1530/EJE-10-0930.) 4. Imperato-McGinley J, Zhu YS. Androgens and male physiology: the syndrome of 5α-reductase-2 deficiency. Mol Cell Endocrinol 2002;198:51–59 5. Wilson JD, Griffin JE, Russel DW. Steroid 5-α-reductase 2 deficiency. Endocrine Reviews 1993;14:577–593. 6. Hochberg Z, Chayen R, Reiss N, Falik Z, Makler A, Munichor M, Farkas A, Goldfarb H, Ohana N, Hiort O. Clinical, biochemical, and genetic findings in a large pedigree of male and female patients with 5 alpha-reductase 2 deficiency. Journal of Clinical Endocrinology and Metabolism 1996;81:2821-2827. 7. Hiort O, Willenbring H, Albers N, Hecker W, Engert J, Dibbelt L, Sinnecker GH. Molecular genetic analysis and human chorionic gonadotropin stimulation tests in the diagnosis of prepubertal patients with partial 5a-reductase 2 deficiency. European Journal of Pediatrics 1996;155:445-451. 8. Sinnecker GH, Hiort O, Dibbelt L, Albers N, Dorr HG, Hauss H, Heinrich U, Hemminghaus M, Hoepffner W, Holder M, Schnabel D, Kruse K. Phenotypic classification of male pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency. American Journal of Medical Genetics 1996;63:223-30. 9. Chávez B, Ramos L, Gómez R, Vilchis F. 46,XY disorder of sexual development resulting from a novel monoallelic mutation (p.Ser31Phe) in the steroid 5α-reductase type-2 (SRD5A2) gene. Molecular Genetics & Genomic Medicine 2014;2:292-6. (doi: 10.1002/mgg3.76.) 10. Di Marco C, Bulotta AL, Varetti C, Dosa L, Michelucci A, Baldinotti F, Meucci D, Castagnini C, Lo Rizzo C, Di Maggio G, Simi P, Mari F, Bertelloni S, Renieri A, Messina M. Ambiguous external genitalia due to defect of 5-α-reductase in seven Iraqi patients: prevalence of a novel mutation. Gene 2013;10:490-493. (doi: 10.1016/j.gene.2013.04.070.) 11. Costa,E.,Domenice,S., Sircili,M. Inacio M, Mendonca BB. DSD due to 5 alpha reductase 2 deficiency: from diagnosis to long term outcome. Seminars in Reproductive Medicine 2012;30:427-431. (doi: 10.1055/s-0032-1324727.) 12. Boudon C, Lobaccaro JM, Lumbroso S, Ogur G, Ocal G, Belon C, Sultan C. A new deletion of the 5 alpha-reductase type 2 gene in a Turkish family with 5 alpha-reductase deficiency. Clin Endocrinol 1995 Aug;43: 183-8. 13. Adiyaman PB, Öcal G, Çetinkaya E, Akar N, Uysal A, Duman T, Evliyaoǧlu O, Aycan Z, Lumbroso S, Sultan C, Berberoǧlu M. 5α steroid reductase deficiency in Turkey. Pediatric Endocrinology Reviews. 2006;3:462-469. 14. Cohen-Kettenis PT. Gender change in 46,XY persons with 5alpha-reductase-2 deficiency and 17beta-hydroxysteroid dehydrogenase-3 deficiency. Archives of Sexual Behavior 2005;34:399-410. 15. Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE. Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science 1974;27:1213-1215. 16. Labrie F, Sugimoto Y, Luu-The V, Simard J, Lachance Y, Bachvarov D, Leblanc G, Durocher F, Paquet N. Structure of human type II 5 alphareductase gene. Endocrinology 1992;131:1571-1573. 17. Bertha Chávez, Luis Ramos, Rita Gómez, and Felipe Vilchis. 46,XY disorder of sexual development resulting from a novel monoallelic mutation (p.Ser31Phe) in the steroid 5α-reductase type-2 (SRD5A2) gene. Molecular Genetics & Genomic Medicine 2014;2:292–296. (doi: 10.1002/mgg3.76.) 18. Wilson JD. Androgens, androgen receptors, and male gender role behavior. Hormones and Behavior 2001;40:358–366. 19. Carla Costa, Cíntia Castro-Correia, Alda Mira-Coelho, Bessa Monteiro, Joaquim Monteiro, Ieuan Hughes, and Manuel Fontoura. The dilemma of the gender assignment in a Portuguese adolescent with disorder of sex development due to 17β-hydroxysteroid-dehydrogenase type 3 enzyme deficiency. Endocrinol Diabetes Metab Case Reports 2014; 2014:140064. (DOI: 10.1530/EDM-14-0064). 20. Imperato-McGinley J, Peterson RE, Gautier T, Sturla E. Androgens and the evolution of male-gender identity among male pseudohermaphrodites with 5α-reductase deficiency. The New England Journal of Medicine 1979;31:1233–1237. 21. Soheir S. Abou El-Ella, Maha A. Tawfik, Wafaa M. Abo El-Fotoh, Ahmed Sh. Abo Howla. Genetic evaluation of children with ambiguous genitalia. Menoufia Medical Journal 2016;29:79–88.