Molecular Characterization of 6 Unrelated Italian Patients With 5α‐Reductase Type 2 Deficiency

Baldinotti, Fulvia; Majore, Silvia; Fogli, Antonella; Marrocco, Giacinto; Ghirri, Paolo; Vuerich, Marco; Tumini, Stefano; Boscherini, B; Vetri, Mario; Scommegna, Salvatore; Rinaldi, Rosanna; Simi, Paolo; Grammatico, Paola

doi:10.2164/jandrol.107.002592

Cited by 44 publications

(36 citation statements)

References 39 publications

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“…Though the first proposed value was 20, Walter et al suggested 8.5 after hCG stimulation as a much more reliable cutoff value [24,64,65]. 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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“…However, equivocal or false-negative T/DHT results are not uncommonly reported (2)(3)(4)(5)(6). Alternative approaches in diagnosing 5ARD include the use of urinary steroid profiling (USP) (7 ) and mutational analysis of SRD5A2 (8 ).…”

Section: ␣-Reductase 2 Is a Membrane-bound Nadphdependent Microsomalmentioning

confidence: 99%

Diagnosis of 5α-Reductase 2 Deficiency: Is Measurement of Dihydrotestosterone Essential?

Chan¹,

But²,

Lee³

et al. 2013

Clinical Chemistry

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BACKGROUND 5α-Reductase 2 deficiency (5ARD) is a known cause of 46,XY disorders of sex development (DSD). Traditionally, the diagnosis relies on dihydrotestosterone (DHT) measurement, but the results are often equivocal, potentially leading to misdiagnosis. We reviewed alternative approaches for diagnosis of 5ARD. METHODS We conducted a retrospective review of the results of urinary steroid profiling (USP) by GC-MS and mutational analysis of SRD5A2 [steroid-5-alpha-reductase, alpha polypeptide 2 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 2)] by PCR and direct DNA sequencing of all 46,XY DSD patients referred to our laboratory with biochemical and/or genetic findings compatible with 5ARD. We also performed a literature review on the laboratory findings of all 5ARD cases reported in the past 10 years. RESULTS Of 16 patients diagnosed with 5ARD between January 2003 and July 2012, 15 underwent USP, and all showed characteristically low 5α- to 5β-reduced steroid metabolite ratios. Four patients had DHT measured, but 2 did not reach the diagnostic cutoff. In all 12 patients who underwent genetic analysis, 2 mutations of the SRD5A2 gene were detected to confirm the diagnosis. Twenty-four publications involving 149 patients with 5ARD were published in the review period. Fewer than half of these patients had DHT tested. Nearly 95% of them had the diagnosis confirmed genetically. CONCLUSIONS 5ARD can be confidently diagnosed by USP at 3 months postnatally and confirmed by mutational analysis of SRD5A2. Interpretation of DHT results may be problematic and is not essential in the diagnosis of 5ARD. We propose new diagnostic algorithms for 46,XY DSD.

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“…[20] Gen seviyesinde erkek infertilitesi, protamin gen mutasyonları [21,22] , 5-alfa redüktaz eksikliği [23] , androjen reseptörü gen mutasyonları [24,25] ve CFTR gen mutasyonlarıyla bağlantılıdır.…”

Section: Discussionunclassified

Kistik fibrozis transmembran regülatör (CFTR) genindeki M470V polimorfizmi ve erkek infertilitesi

Gökçe¹,

Gül²

2017

Androl Bul

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GİRİŞErkek infertilitesi; korunmasız cinsel ilişkiye rağmen bir yı-lın sonunda konsepsiyon meydana gelmemesi veya çocuk sahibi olunamaması olarak tanımlanmaktadır.[1] Evli çiftlerin yaklaşık %10-15'i bebek sahibi olabilmek için tıbbi yardım ABSTRACT OBJECTIVE: Cystic fibrosis (CF) is one of the conditions that cause male infertility. CF is caused infertility in men by usually resulting congenital bilateral vas deferens agenesis (CBVDA). However, studies on how mutations and polymorphisms in CF gene affect spermatogenesis are limited. In this study, we aimed to investigate the association of severe oligozoospermia or nonobstructive azoospermia (NOA) with M470V polymorphism in the CF gene in non-CBVDA males. MATERIAL and METHODS:Thirty-three patients with severe oligozoospermia or NAO who were admitted to our andrology clinic because of infertility were enrolled in the study. Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene analysis was performed to evaluate the presence of M470V polymorphism. RESULTS:The mean age was 34.3 years. 13 of 33 patients (39.4%) had NOA, and 20 (60.4%) had severe oligozoospermia. M470V polymorphism was present in 19 (58%) patients, 8 of them were in the NOA group (62%) and 11 (55%) were in the oligozoospermia group. The frequency of M470V polymorphism in our patient group was found higher than expected in the population when compared with the rates reported in previous studies (28-47%) with healthy population. CONCLUSION:The results of this study suggest that increased M470V polymorphism in individuals with severe oligozoospermia or NOA may also have effects on spermatogenesis other than CBVDA. However, there is a need for more extensive studies on this topic.

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Molecular Characterization of 6 Unrelated Italian Patients With 5α‐Reductase Type 2 Deficiency

Cited by 44 publications

References 39 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

Diagnosis of 5α-Reductase 2 Deficiency: Is Measurement of Dihydrotestosterone Essential?

Kistik fibrozis transmembran regülatör (CFTR) genindeki M470V polimorfizmi ve erkek infertilitesi

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