Clinical Characterization and Analysis of the &lt;i&gt;SRD5A2 &lt;/i&gt;Gene in Six Korean Patients with 5α-Reductase Type 2 Deficiency

Ko, Jung Min; Cheon, Chong Kun; Kim, Gu-Hwan; Kim, Sung Hoon; Kim, Kun Suk; Yoo, Han-Wook

doi:10.1159/000271915

Cited by 29 publications

(38 citation statements)

References 50 publications

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“…The p.G203S mutation on one allele found in all 3 patients was previously reported in patients from Mexico [15,16], Thailand [17] and Korea [18]. The same mutation was also reported previously in 8 Chinese hypospadia patients [19].…”

Section: Discussionsupporting

confidence: 77%

A Novel SRD5A2 Mutation with Loss of Function Identified in Chinese Patients with Hypospadias

et al. 2011

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Objective: To investigate the functional change of SRD5A2 gene mutations identified in patients with 5α-reductase type 2 deficiency. Patients and Methods: Three unrelated subjects born with ambiguous genitalia were included. All patients were initially reared as girls, but they gradually exhibited variable degrees of virilization at puberty without breast development, followed by a change of gender role. Sequencing analysis of the SRD5A2 gene was performed and enzymatic activities of 5α-reductase type 2 were assessed. Results: Three compound heterozygous mutations in the SRD5A2 gene were identified: patient 1 with p.G203S/ c.655delT, patient 2 with p.Q6X/p.G203S, and patient 3 with p.G203S/c.755_756insT. Heterozygosity for the p.V89L polymorphism was also found in patients 2 and 3. The c.655delT mutation led to a complete loss of the enzymatic activity, whereas mutants p.G203S and c.755_756insT resulted in a reduction of the enzymatic activities by 60 and 90%, respectively. Conclusion: Two frameshift heterozygous mutations, c.655delT and c.755_756insT, led to a dramatic reduction in 5α-reductase activity, and the latter had not been reported previously. In addition, the heterozygous mutation (p.G203) identified in the 3 patients presumably suggests a founder effect in the Chinese population and may explain the similarity in phenotype among the patients.

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Section: Discussionsupporting

confidence: 77%

A Novel SRD5A2 Mutation with Loss of Function Identified in Chinese Patients with Hypospadias

et al. 2011

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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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“…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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Clinical Characterization and Analysis of the <i>SRD5A2 </i>Gene in Six Korean Patients with 5α-Reductase Type 2 Deficiency

Cited by 29 publications

References 50 publications

A Novel SRD5A2 Mutation with Loss of Function Identified in Chinese Patients with Hypospadias

A Novel SRD5A2 Mutation with Loss of Function Identified in Chinese Patients with Hypospadias

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?

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