Clinical, Hormonal, and Genetic Characteristics of 5α-Reductase Type 2 Deficiency in 103 Chinese Patients

Liu, Qingxu; Yin, Xiaoqin; Пин, Ли

doi:10.1016/j.eprac.2022.06.002

Cited by 2 publications

(17 citation statements)

References 30 publications

(39 reference statements)

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“…Currently, it is well established that the proportion of homozygous mutations is higher (60–70%) than that of heterozygous mutations in 5αRD2 [ 10 , 12 , 14 , 19 , 36 ]; however, an opposite ratio of homozygous (31.6%) and compound heterozygous mutations (68.4%) were identified in the present study. This is consistent with several recent East Asian cohort studies wherein the frequency of compound heterozygosity (55–80%) was higher than that of homozygosity [ 7 , 8 , 11 , 13 , 19 ]. In addition, although the mutations were distributed along all exons, exons 1 and 4 were considered hot spots in SRD5A2 gene mutations [ 8 , 10 , 11 , 12 , 13 , 14 , 15 ].…”

Section: Discussionsupporting

confidence: 93%

“…This is consistent with several recent East Asian cohort studies wherein the frequency of compound heterozygosity (55–80%) was higher than that of homozygosity [ 7 , 8 , 11 , 13 , 19 ]. In addition, although the mutations were distributed along all exons, exons 1 and 4 were considered hot spots in SRD5A2 gene mutations [ 8 , 10 , 11 , 12 , 13 , 14 , 15 ]. However, in Turkish population studies [ 15 , 37 ], exon 3 has also been identified as a hot spot.…”

Section: Discussionsupporting

confidence: 93%

“…There have been many attempts to elucidate a genotype-phenotype link in 5αRD2 [ 8 , 10 , 11 , 12 , 13 ], as the wide range of phenotypes is likely attributable to individual genetic backgrounds. However, most studies have not established a genotype-phenotype correlation [ 7 , 12 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

“…From a structural perspective, there are five categories of SRD5A2 gene mutations: (1) catalytic site mutations, (2) NADPH-binding residue mutations, (3) structure-destabilizing mutations, (4) helix-breaking mutations, and (5) small to bulky residue (destabilizing) mutations [ 21 ]. For example, the p.R227Q variant of the SRD5A2 gene, one of the founder mutations in East Asians [ 7 , 8 , 13 , 22 ], reduces the activity of SRD5A2 by disrupting cofactor (NADPH) binding [ 20 , 21 ]. Furthermore, the p.H231R variant, which is widely distributed among Caucasians [ 10 ], is also associated with the NADPH binding residue [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, the p.Q126R, p.P181L, and p.P212R variants also belong to this category [ 21 ]. The p.G203S variant, which is another frequently reported mutation in East Asian patients [ 8 , 13 , 19 , 23 , 24 ], belongs to the small to bulky residue category along with p.G34R and p.G196S [ 21 ]. However, an evaluation of the genotype-phenotype correlation from a SRD5A2 gene structural perspective is yet to be demonstrated.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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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Effects of Androgen Treatment on Growth in Patients with 5-α-Reductase Type 2 Deficiency

Lee

Kim

et al. 2023

JPM

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Background: Patients with 5-α-reductase type 2 deficiency (5αRD2) require androgen treatment for the growth of normal male external genitalia. Since limited research has been conducted on the effects of androgen treatment on height in individuals with 5αRD2, we investigated the effect of androgen treatment on bone age (BA) and the height status in children with 5αRD2. Methods: Of the 19 participants who were followed up for an average of 10.6 years, 12 received androgen treatment. BA and height standard deviation scores (SDS) were compared between the treatment and non-treatment groups, as well as between the dihydrotestosterone (DHT) and testosterone enanthate (TE) treatment groups. Results: Despite the above-average height of the 19 patients with 5αRD2, the height SDS relative to BA (htSDS-BA) was below average, particularly in the androgen treatment group. DHT treatment did not lead to an increase in BA or htSDS-BA, whereas TE treatment resulted in BA advancement and decreased htSDS-BA, especially in the prepubertal period. Conclusions: DHT treatment is more favorable for height than TE treatment in patients with 5αRD2, particularly during the prepubertal period. Therefore, age and the type of androgen used should be carefully considered to minimize the risk of height reduction in these patient groups.

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Clinical, Hormonal, and Genetic Characteristics of 5α-Reductase Type 2 Deficiency in 103 Chinese Patients

Cited by 2 publications

References 30 publications

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

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

Effects of Androgen Treatment on Growth in Patients with 5-α-Reductase Type 2 Deficiency

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