Clinical characteristics and genotype‐phenotype correlations of 130 Chinese children in a high‐homogeneity single‐center cohort with 5α‐reductase 2 deficiency
Abstract Background Patients with steroid 5α‐reductase 2 deficiency (5α‐RD) caused by SRD5A2 (OMIM #607306) variants present variable genotypes and phenotypes. The genotype‐phenotype correlations remain unclear. Methods We investigated genotype‐phenotype correlations of SRD5A2 variants in a large Ch...
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| Format: | Article |
| Language: | English |
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Wiley
2020-10-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.1431 |
| _version_ | 1797300977924046848 |
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| author | Lijun Fan Yanning Song Michel Polak Lele Li Xiaoya Ren Beibei Zhang Di Wu Chunxiu Gong |
| author_facet | Lijun Fan Yanning Song Michel Polak Lele Li Xiaoya Ren Beibei Zhang Di Wu Chunxiu Gong |
| author_sort | Lijun Fan |
| collection | DOAJ |
| description | Abstract Background Patients with steroid 5α‐reductase 2 deficiency (5α‐RD) caused by SRD5A2 (OMIM #607306) variants present variable genotypes and phenotypes. The genotype‐phenotype correlations remain unclear. Methods We investigated genotype‐phenotype correlations of SRD5A2 variants in a large Chinese single‐center cohort. Phenotypes were categorized using the external masculinization score (EMS), urethral meatus and gonad position, and penile length‐standard deviation score. Results Of the 130 included patients, 113 had hypospadias, and 17 had a normal urethral meatus position. Testosterone/dihydrotestosterone (T/DHT) values were not significantly associated with phenotypic severity (p = 0.539–0.989). Of the 31 SRD5A2 variants, including 10 novel variants, p.R227Q was the most prevalent (39.62%), followed by p.Q6* (16.92%), p.R246Q (13.46%), and p.G203S (10.38%). Compared to biallelic missense mutations, biallelic nonsense mutations were associated with a lower EMS and urethral meatus score (p = 0.009 and p = 0.024, respectively). Patients homozygous for p.R227Q exhibited mild and variable phenotypes, while those homozygous for p.Q6*, p.R246Q, or p.G203S showed consistently severe phenotypes. The phenotypes were variable and milder in patients with compound heterozygosity for p.R227Q and these mutations. Conclusion T/DHT does not predict phenotype severity. The most prevalent SRD5A2 variant in Han Chinese is p.R227Q, which is associated with milder phenotypes and greater phenotypic variability. SRD5A2 variants may significantly influence phenotypic variation. |
| first_indexed | 2024-03-07T23:15:43Z |
| format | Article |
| id | doaj.art-269a201041ac49b9b6b395b11e751513 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:15:43Z |
| publishDate | 2020-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-269a201041ac49b9b6b395b11e7515132024-02-21T12:03:03ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-10-01810n/an/a10.1002/mgg3.1431Clinical characteristics and genotype‐phenotype correlations of 130 Chinese children in a high‐homogeneity single‐center cohort with 5α‐reductase 2 deficiencyLijun Fan0Yanning Song1Michel Polak2Lele Li3Xiaoya Ren4Beibei Zhang5Di Wu6Chunxiu Gong7Department of Endocrinology, Genetics, Metabolism Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s Health Beijing ChinaDepartment of Endocrinology, Genetics, Metabolism Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s Health Beijing ChinaService d'endocrinologie, gynécologie et diabétologiepédiatriques Hôpitaluniversitaire Necker Enfants Maladesuniversité de ParisIMAGINE institute Paris FranceDepartment of Endocrinology, Genetics, Metabolism Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s Health Beijing ChinaDepartment of Endocrinology, Genetics, Metabolism Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s Health Beijing ChinaDepartment of Endocrinology, Genetics, Metabolism Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s Health Beijing ChinaDepartment of Endocrinology, Genetics, Metabolism Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s Health Beijing ChinaDepartment of Endocrinology, Genetics, Metabolism Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s Health Beijing ChinaAbstract Background Patients with steroid 5α‐reductase 2 deficiency (5α‐RD) caused by SRD5A2 (OMIM #607306) variants present variable genotypes and phenotypes. The genotype‐phenotype correlations remain unclear. Methods We investigated genotype‐phenotype correlations of SRD5A2 variants in a large Chinese single‐center cohort. Phenotypes were categorized using the external masculinization score (EMS), urethral meatus and gonad position, and penile length‐standard deviation score. Results Of the 130 included patients, 113 had hypospadias, and 17 had a normal urethral meatus position. Testosterone/dihydrotestosterone (T/DHT) values were not significantly associated with phenotypic severity (p = 0.539–0.989). Of the 31 SRD5A2 variants, including 10 novel variants, p.R227Q was the most prevalent (39.62%), followed by p.Q6* (16.92%), p.R246Q (13.46%), and p.G203S (10.38%). Compared to biallelic missense mutations, biallelic nonsense mutations were associated with a lower EMS and urethral meatus score (p = 0.009 and p = 0.024, respectively). Patients homozygous for p.R227Q exhibited mild and variable phenotypes, while those homozygous for p.Q6*, p.R246Q, or p.G203S showed consistently severe phenotypes. The phenotypes were variable and milder in patients with compound heterozygosity for p.R227Q and these mutations. Conclusion T/DHT does not predict phenotype severity. The most prevalent SRD5A2 variant in Han Chinese is p.R227Q, which is associated with milder phenotypes and greater phenotypic variability. SRD5A2 variants may significantly influence phenotypic variation.https://doi.org/10.1002/mgg3.1431disorders of sex developmentgenotype‐phenotype correlationSRD5A2 genesteroid 5α‐reductase type 2 deficiency |
| spellingShingle | Lijun Fan Yanning Song Michel Polak Lele Li Xiaoya Ren Beibei Zhang Di Wu Chunxiu Gong Clinical characteristics and genotype‐phenotype correlations of 130 Chinese children in a high‐homogeneity single‐center cohort with 5α‐reductase 2 deficiency Molecular Genetics & Genomic Medicine disorders of sex development genotype‐phenotype correlation SRD5A2 gene steroid 5α‐reductase type 2 deficiency |
| title | Clinical characteristics and genotype‐phenotype correlations of 130 Chinese children in a high‐homogeneity single‐center cohort with 5α‐reductase 2 deficiency |
| title_full | Clinical characteristics and genotype‐phenotype correlations of 130 Chinese children in a high‐homogeneity single‐center cohort with 5α‐reductase 2 deficiency |
| title_fullStr | Clinical characteristics and genotype‐phenotype correlations of 130 Chinese children in a high‐homogeneity single‐center cohort with 5α‐reductase 2 deficiency |
| title_full_unstemmed | Clinical characteristics and genotype‐phenotype correlations of 130 Chinese children in a high‐homogeneity single‐center cohort with 5α‐reductase 2 deficiency |
| title_short | Clinical characteristics and genotype‐phenotype correlations of 130 Chinese children in a high‐homogeneity single‐center cohort with 5α‐reductase 2 deficiency |
| title_sort | clinical characteristics and genotype phenotype correlations of 130 chinese children in a high homogeneity single center cohort with 5α reductase 2 deficiency |
| topic | disorders of sex development genotype‐phenotype correlation SRD5A2 gene steroid 5α‐reductase type 2 deficiency |
| url | https://doi.org/10.1002/mgg3.1431 |
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