title: Phenotype, genotype and gender identity in a large cohort of patients from India with 5α-reductase 2 deficiency.
abstract: Deficiency of the 5α-reductase 2 enzyme impairs the conversion of testosterone to dihydrotestosterone (DHT) and differentiation of external genitalia, seminal vesicles and prostate in males. The present study describes the phenotype, genotype and gender identity in a large cohort of patients with 5αRD2. All patients underwent detailed clinical evaluation, hormonal profile, karyotyping and molecular analysis of the SRD5A2 gene. The molecular analysis of the SRD5A2 gene showed the presence of mutant alleles in 24 patients. We found 6 novel mutations IVS(1-2) T>C, p.A52T, 188-189insTA, 904-905ins A, p.A12T and p.E57X in our patients. All patients had ambiguous genitalia and the degrees of under-virilization ranged from penoscrotal hypospadias and microphallus to clitoromegaly. The position of gonads was variable in patients with same mutation. All the patients with mutations in the SRD5A2 gene had male gender identity. Those reared as female had gender dysphoria and underwent gender reassignment. Though a specific genotype-phenotype correlation could not be established in our patient but confirming the diagnosis of 5αRD2 with assessment of the SRD5A2 gene may help in appropriate gender assignment.
authors.affiliation: Department of Endocrinology & Metabolism, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: I
authors.initials: I
authors.lastname: Shabir
authors.affiliation: Department of Endocrinology & Metabolism, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: M L
authors.initials: ML
authors.lastname: Khurana
authors.affiliation: Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: A A
authors.initials: AA
authors.lastname: Joseph
authors.affiliation: Department of Endocrinology & Metabolism, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: M
authors.initials: M
authors.lastname: Eunice
authors.affiliation: Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: M
authors.initials: M
authors.lastname: Mehta
authors.affiliation: Department of Endocrinology & Metabolism, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: A C
authors.initials: AC
authors.lastname: Ammini
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency* / Q000235:genetics*; D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D058490:Disorder of Sex Development, 46,XY / Q000201:enzymology / Q000235:genetics* / Q000523:psychology / Q000628:therapy; D005260:Female; D000068116:Gender Dysphoria / Q000201:enzymology / Q000235:genetics* / Q000523:psychology / Q000628:therapy; D005783:Gender Identity; D020022:Genetic Predisposition to Disease; D006728:Hormones / Q000097:blood; D006801:Humans; D007194:India; D007223:Infant; D059785:Karyotype; D007621:Karyotyping; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D057829:Gender-Affirming Procedures; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; D006728:Hormones; D008565:Membrane Proteins; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human
keywords: 5α-reductase 2 deficiency; SRD5A2 gene; dihydrotestosterone; testosterone