Primary amenorrhea in four adolescents revealed 5α-reductase deficiency confirmed by molecular analysis

Maı̈moun, Laurent; Philibert, Pascal; Bouchard, Philippe; Öçal, Gönül; Leheup, Bruno; Fénichel, Patrick; Servant, Nadège; Paris, Florentin; Sultan, Charles

doi:10.1016/j.fertnstert.2010.08.007

Cited by 19 publications

(10 citation statements)

References 34 publications

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“…However, in many instances, this method has failed as a good predictor and various other approaches have been proposed [22,39,41,45,49], urinary steroid profiling (UPS) and gene mutation analysis being two alternatives. Chan et al suggested that UPS results can be misinterpreted; thus, molecular [25,39,40] p.G115D/p.G115D 5 2.60 0.55 [22,39,41,42] analysis was considered the most effective diagnostic method also taking into account the small size of the gene makes the diagnostic procedure easier [50].…”

Section: Diagnosismentioning

confidence: 99%

5-α-Reductase type 2 deficiency: is there a genotype-phenotype correlation? A review

et al. 2018

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5-α-Reductase type 2 enzyme catalyzes the conversion of testosterone into dihydrotestosterone, a potent androgen responsible for male sexual development during the fetal period and later during puberty. Its deficiency causes an autosomal recessive disorder of sex development characterized by a wide range of under-virilization of external genitalia in patients with a 46,XY karyotype. Mutations in the SRD5A2 gene cause 5-α-Reductase deficiency; although it is an infrequent disorder, it has been reported worldwide, with mutational heterogeneity. Furthermore, it has been proposed that there is no genotype-phenotype correlation, even in patients carrying the same mutation. The aim of this review was to perform an extensive search in various databases and to select those articles with a comprehensive genotype and phenotype description of the patients, classifying their phenotypes using the external masculinization score (EMS). Thus, it was possible to objectively compare the eventual genotypephenotype correlation between them. The analysis showed that for most of the studied mutations no correlation can be established, although the specific location of the mutation in the protein has an effect on the severity of the phenotype. Nevertheless, even in patients carrying the same homozygous mutation, a variable phenotype was observed, suggesting that additional genetic factors might be influencing it. Due to the clinical variability of the disorder, an accurate diagnosis and adequate medical management might be difficult to carry out, as is highlighted in the review.

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Section: Diagnosismentioning

confidence: 99%

5-α-Reductase type 2 deficiency: is there a genotype-phenotype correlation? A review

et al. 2018

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“…11,40,43,44 Likewise, identical mutations have been found in individuals with widely divergent geographic and ethnic backgrounds, suggesting the existence of mutational hot spots in this gene. 45 In few 46,XY DSD patients with 5-α reductase 2 deficiency diagnosed by clinical and hormonal findings no mutations were identified in the SRD5A2. 15,17,24,41 Treatment A careful psychological evaluation must be performed before any surgical or hormonal treatment in these patients.…”

Section: Srd5a2 Mutationsmentioning

confidence: 99%

DSD Due to 5α-Reductase 2 Deficiency - from Diagnosis to Long Term Outcome

et al. 2012

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Most of the patients with 5α-RD 2 deficiency are reared in the female social sex due to their severely undervirilized external genitalia but ~60% who have not been submitted to orchiectomy in childhood undergo male social sex change at puberty. In our cohort of 30 cases from 18 families, all subjects were registered in the female social sex except for two children-one who had an affected uncle and the other who was diagnosed before being registered. The majority of the patients were satisfied with the long-term results of their treatment and surprisingly, penile length was not associated with satisfactory or unsatisfactory sexual activity. Steroid 5α-RD2 deficiency should be included in the differential diagnosis of all newborns with 46,XY DSD with normal testosterone production before gender assignment or any surgical intervention because these patients should be considered males at birth.

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“…Nevertheless, four variants belong to the catalytic site mutation category [ 21 ], and, among them, the pathogenic mechanisms of p.E57 and p.Y91 have been identified through crystal structures [ 20 ]. Although there has been a limited number of cases presenting mutations of these sites, their phenotypes are close to the female phenotype with low EMSs [ 8 , 26 , 27 , 28 ]. Similarly, variants belonging to the helix-breaking category exhibit severe phenotypes.…”

Section: Discussionmentioning

confidence: 99%

The Genotype-Phenotype Correlation in Human 5α-Reductase Type 2 Deficiency: Classified and Analyzed from a SRD5A2 Structural Perspective

Seo

Shin

Kim

et al. 2023

IJMS

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The phenotype of the 5α-reductase type 2 deficiency (5αRD2) by the SRD5A2 gene mutation varies, and although there have been many attempts, the genotype-phenotype correlation still has not yet been adequately evaluated. Recently, the crystal structure of the 5α-reductase type 2 isozyme (SRD5A2) has been determined. Therefore, the present study retrospectively evaluated the genotype-phenotype correlation from a structural perspective in 19 Korean patients with 5αRD2. Additionally, variants were classified according to structural categories, and phenotypic severity was compared with previously published data. The p.R227Q variant, which belongs to the NADPH-binding residue mutation category, exhibited a more masculine phenotype (higher external masculinization score) than other variants. Furthermore, compound heterozygous mutations with p.R227Q mitigated phenotypic severity. Similarly, other mutations in this category showed mild to moderate phenotypes. Conversely, the variants categorized as structure-destabilizing and small to bulky residue mutations showed moderate to severe phenotypes, and those categorized as catalytic site and helix-breaking mutations exhibited severe phenotypes. Therefore, the SRD5A2 structural approach suggested that a genotype-phenotype correlation does exist in 5αRD2. Furthermore, the categorization of SRD5A2 gene variants according to the SRD5A2 structure facilitates the prediction of the severity of 5αRD2 and the management and genetic counseling of patients affected by it.

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Primary amenorrhea in four adolescents revealed 5α-reductase deficiency confirmed by molecular analysis

Cited by 19 publications

References 34 publications

5-α-Reductase type 2 deficiency: is there a genotype-phenotype correlation? A review

5-α-Reductase type 2 deficiency: is there a genotype-phenotype correlation? A review

DSD Due to 5α-Reductase 2 Deficiency - from Diagnosis to Long Term Outcome

The Genotype-Phenotype Correlation in Human 5α-Reductase Type 2 Deficiency: Classified and Analyzed from a SRD5A2 Structural Perspective

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