Coexistence of SRY, DHX37 and POR gene variants in a patient with 46,XY disorder of sex development
-
Ayse Ozden
,
Hakan Doneray
,
Ayberk Turkyilmaz
and
Binali Firinci
Abstract
Objectives
Here we present a case of 46,XY disorder of sex development (DSD) in which three variants were detected in the SRY, DHX37, and POR genes.
Case presentation
A patient with 46,XY karyotype and female phenotype presented at 15 years 3 months of age due to absence of puberty. She exhibited facial signs such as midfacial hypoplasia, long face, proptosis, bulbous nose, mild prognathism and skeletal signs such as scoliosis, pectus carinatum, arachnodactyly and her sex development remained prepubertal. The patient was found to have hypergonadotropic hypogonadism, elevation of 17-OH progesterone and progesterone levels, low anti-mullerian hormone and inhibin B levels, and absence of gonads and a hypoplastic uterus on pelvic ultrasound. Whole exome sequencing revealed a novel hemizygous missense variant in the SRY gene (c.247C>T, p.Pro83Ser), a homozygous missense variant in the POR gene (c.1355C>T, p.Pro452Leu), and a novel heterozygous missense variant in the DHX37 gene (c.1325A>G, p.His442Arg).
Conclusions
Our patient is the first case in which the coexistence of variants in the SRY, DHX37 and POR genes was detected. This case suggests that a combined phenotype characterized by DSD and alterations in adrenal function may result from genetic variants in the SRY, DHX37 and POR genes involved in gonadal development and synthesis of adrenal hormones.
-
Research ethics: Not applicable.
-
Informed consent: Not applicable.
-
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Use of Large Language Models, AI and Machine Learning Tools: None declared.
-
Conflict of interest: The authors state no conflict of interest.
-
Research funding: None declared.
-
Data availability: Not applicable.
References
1. Elzaiat, M, McElreavey, K, Bashamboo, A. Genetics of 46,XY gonadal dysgenesis. Best Pract Res Clin Endocrinol Metabol 2022;36:101633. https://doi.org/10.1016/j.beem.2022.101633.Search in Google Scholar PubMed
2. De Oliveira, FR, Guaragna, MS, Maciel-Guerra, AT, Barros, BA, de Mello, MP, Guerra-Junior, G, et al.. DHX37 and the implications in disorders of sex development: an update review. Horm Res Paediatr 2023;23. https://doi.org/10.1159/000535969. Online ahead of print.Search in Google Scholar PubMed
3. Rocha, VB, Guerra-Júnior, G, Marques-de-Faria, AP, de Mello, MP, Maciel-Guerra, AT. Complete gonadal dysgenesis in clinical practice: the 46,XY karyotype accounts for more than one third of cases. Fertil Steril 2011;96:1431–4. https://doi.org/10.1016/j.fertnstert.2011.09.009.Search in Google Scholar PubMed
4. McElreavey, K, Pailhoux, E, Bashamboo, A. DHX37 and 46,XY DSD: a new ribosomopathy? Sex Dev 2022;16:194–206. https://doi.org/10.1159/000522004.Search in Google Scholar PubMed
5. Dean, B, Chrisp, GL, Quartararo, M, Maguire, AM, Hameed, S, King, BR, et al.. P450 oxidoreductase deficiency: a systematic review and meta-analysis of genotypes, phenotypes, and their relationships. J Clin Endocrinol Metab 2020;105:dgz255. https://doi.org/10.1210/clinem/dgz255.Search in Google Scholar PubMed
6. Wang, X, Xue, M, Zhao, M, He, F, Li, C, Li, X. Identification of a novel mutation (Ala66Thr) of SRY gene causes XY pure gonadal dysgenesis by affecting DNA binding activity and nuclear import. Gene 2018;651:143–51. https://doi.org/10.1016/j.gene.2018.01.076.Search in Google Scholar PubMed
7. de Oliveira, FR, Mazzola, TN, de Mello, MP, Francese-Santos, AP, Lemos-Marini, SHV, Maciel-Guerra, AT, et al.. DHX37 and NR5A1 variants identified in patients with 46,XY partial gonadal dysgenesis. Life 2023;13:1093. https://doi.org/10.3390/life13051093.Search in Google Scholar PubMed PubMed Central
8. McElreavey, K, Jorgensen, A, Eozenou, C, Merel, T, Bignon-Topalovic, J, Tan, DS, et al.. Pathogenic variants in the DEAH-box RNA helicase DHX37 are a frequent cause of 46,XY gonadal dysgenesis and 46,XY testicular regression syndrome. Genet Med 2020;22:150–9. https://doi.org/10.1038/s41436-019-0606-y.Search in Google Scholar PubMed PubMed Central
9. da Silva, TE, Gomes, NL, Lerario, AM, Keegan, CE, Nishi, MY, Carvalho, FM, et al.. Genetic evidence of the association of DEAH-box helicase 37 defects with 46,XY gonadal dysgenesis spectrum. J Clin Endocrinol Metab 2019;104:5923–34. https://doi.org/10.1210/jc.2019-00984.Search in Google Scholar PubMed
10. Yang, H, Ma, X, Tian, H, Yuan, J, Wu, D, Dong, G. Two novel heterozygous variants in RecA2 domain of DHX37 cause 46,XY gonadal dysgenesis and testicular regression syndrome. Sex Dev 2023;17:198–202. 202315.10.1159/000534086Search in Google Scholar PubMed PubMed Central
11. Wan, Y, Yu, R, Luo, J, Huang, P, Zheng, X, Sun, L, et al.. A novel DEAH-box helicase 37 mutation associated with differences of sex development. Front Endocrinol 2023;14:1059159. https://doi.org/10.3389/fendo.2023.1059159.Search in Google Scholar PubMed PubMed Central
12. Huang, N, Agrawal, V, Giacomini, KM, Miller, WL. Genetics of P450 oxidoreductase: sequence variation in 842 individuals of four ethnicities and activities of 15 missense mutations. Proc Natl Acad Sci U. S. A 2008;105:1733–8. https://doi.org/10.1073/pnas.0711621105.Search in Google Scholar PubMed PubMed Central
13. Gusmano, C, Cannarella, R, Crafa, A, Barbagallo, F, La Vignera, S, Condorelli, RA, et al.. Congenital adrenal hyperplasia, disorders of sex development, and infertility in patients with POR gene pathogenic variants: a systematic review of the literatüre. J Endocrinol Investig 2023;46:1–14. https://doi.org/10.1007/s40618-022-01849-9.Search in Google Scholar PubMed PubMed Central
Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/jpem-2024-0554).
© 2025 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Reviews
- Pubertal disorders in juvenile idiopathic arthritis: a systemic review
- Hormonal therapy for impaired growth due to pediatric-onset inflammatory bowel disease: a systematic review and meta-analysis with trial sequential analysis
- Mini Review
- Neonatal hypoglycaemia in the offsprings of parents with maturity-onset diabetes of the young (MODY)
- Original Articles
- Cord blood metabolomic profiling in high risk newborns born to diabetic, obese, and overweight mothers: preliminary report
- Impact of Covid-19 on children and adolescents with type 1 diabetes: lifestyle, telecommunication service, and quality of life
- The diagnostic utility of bioelectrical impedance analysis in distinguishing precocious puberty from premature thelarche
- Infant gonadotropins predict spontaneous puberty in girls with Turner syndrome
- Bioinformatics analysis explores key pathways and hub genes in central precocious puberty
- Impact of growth hormone therapy on bone and body composition in prepubertal children with idiopathic short stature
- Presence of hyperandrogenemia in cases evaluated due to menstrual irregularity, the effect of clinical and/or biochemical hyperandrogenemia on polycystic ovary syndrome
- Cardiac function in children with congenital adrenal hyperplasia
- Short Communication
- Clinical and genetic insights into congenital lipoid adrenal hyperplasia: a case series from a tertiary care center in North India
- Case Reports
- Two families, two pathways: a case series of 46, XY DSD with 17α-hydroxylase deficiency and isolated 17,20-lyase deficiency due to novel CYB5A variant
- Coexistence of SRY, DHX37 and POR gene variants in a patient with 46,XY disorder of sex development
- Diabetes, macrocytosis, and skin changes in large-scale mtDNA deletion
Articles in the same Issue
- Frontmatter
- Reviews
- Pubertal disorders in juvenile idiopathic arthritis: a systemic review
- Hormonal therapy for impaired growth due to pediatric-onset inflammatory bowel disease: a systematic review and meta-analysis with trial sequential analysis
- Mini Review
- Neonatal hypoglycaemia in the offsprings of parents with maturity-onset diabetes of the young (MODY)
- Original Articles
- Cord blood metabolomic profiling in high risk newborns born to diabetic, obese, and overweight mothers: preliminary report
- Impact of Covid-19 on children and adolescents with type 1 diabetes: lifestyle, telecommunication service, and quality of life
- The diagnostic utility of bioelectrical impedance analysis in distinguishing precocious puberty from premature thelarche
- Infant gonadotropins predict spontaneous puberty in girls with Turner syndrome
- Bioinformatics analysis explores key pathways and hub genes in central precocious puberty
- Impact of growth hormone therapy on bone and body composition in prepubertal children with idiopathic short stature
- Presence of hyperandrogenemia in cases evaluated due to menstrual irregularity, the effect of clinical and/or biochemical hyperandrogenemia on polycystic ovary syndrome
- Cardiac function in children with congenital adrenal hyperplasia
- Short Communication
- Clinical and genetic insights into congenital lipoid adrenal hyperplasia: a case series from a tertiary care center in North India
- Case Reports
- Two families, two pathways: a case series of 46, XY DSD with 17α-hydroxylase deficiency and isolated 17,20-lyase deficiency due to novel CYB5A variant
- Coexistence of SRY, DHX37 and POR gene variants in a patient with 46,XY disorder of sex development
- Diabetes, macrocytosis, and skin changes in large-scale mtDNA deletion
